{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:53:55Z","timestamp":1790949235591,"version":"4.1.0"},"reference-count":83,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"vor","delay-in-days":85,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK135308-01"],"award-info":[{"award-number":["R01DK135308-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Department of Veterans Affairs"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Commun Signal"],"DOI":"10.1186\/s12964-026-03054-0","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:54:00Z","timestamp":1783572840000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Myofibroblast- specific autophagy drives cyst growth in autosomal dominant polycystic kidney disease"],"prefix":"10.1186","volume":"24","author":[{"given":"Abeda","family":"Jamadar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viji","family":"Remadevi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meekha M","family":"Varghese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haichun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vedant P.","family":"Thakkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indra","family":"Chandrasekar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Xing","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker H.","family":"Haase","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren P.","family":"Wallace","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reena","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"issue":"2","key":"3054_CR1","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1053\/j.ackd.2009.12.001","volume":"17","author":"Y Pei","year":"2010","unstructured":"Pei Y, Watnick T. Diagnosis and screening of autosomal dominant polycystic kidney disease. Adv Chronic Kidney Dis. 2010;17(2):140\u201352.","journal-title":"Adv Chronic Kidney Dis"},{"key":"3054_CR2","doi-asserted-by":"crossref","unstructured":"Chapman AB, Devuyst O, Eckardt KU, Gansevoort RT, Harris T, Horie S, et al. Autosomal-dominant polycystic kidney disease (ADPKD): executive summary from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2015;88(1):17\u201327.","DOI":"10.1038\/ki.2015.59"},{"key":"3054_CR3","doi-asserted-by":"crossref","unstructured":"Fragiadaki M, Macleod FM, Ong ACM. The Controversial Role of Fibrosis in Autosomal Dominant Polycystic Kidney Disease. Int J Mol Sci. 2020;21(23):8936\u201351.","DOI":"10.3390\/ijms21238936"},{"key":"3054_CR4","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1007\/978-3-319-51436-9_12","volume":"60","author":"CJ Song","year":"2017","unstructured":"Song CJ, Zimmerman KA, Henke SJ, Yoder BK. Inflammation and Fibrosis in Polycystic Kidney Disease. Results Probl Cell Differ. 2017;60:323\u201344.","journal-title":"Results Probl Cell Differ"},{"key":"3054_CR5","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1007\/978-981-13-8871-2_5","volume":"1165","author":"C Xue","year":"2019","unstructured":"Xue C, Mei CL. Polycystic Kidney Disease and Renal Fibrosis. Adv Exp Med Biol. 2019;1165:81\u2013100.","journal-title":"Adv Exp Med Biol"},{"issue":"6","key":"3054_CR6","doi-asserted-by":"publisher","first-page":"2299","DOI":"10.1172\/JCI72267","volume":"124","author":"JS Duffield","year":"2014","unstructured":"Duffield JS. Cellular and molecular mechanisms in kidney fibrosis. J Clin Invest. 2014;124(6):2299\u2013306.","journal-title":"J Clin Invest"},{"issue":"3\u20134","key":"3054_CR7","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1007\/s004670000461","volume":"15","author":"AA Eddy","year":"2000","unstructured":"Eddy AA. Molecular basis of renal fibrosis. Pediatr Nephrol. 2000;15(3\u20134):290\u2013301.","journal-title":"Pediatr Nephrol"},{"issue":"3","key":"3054_CR8","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1097\/MNH.0b013e3283521cfa","volume":"21","author":"AB Farris","year":"2012","unstructured":"Farris AB, Colvin RB. Renal interstitial fibrosis: mechanisms and evaluation. Curr Opin Nephrol Hypertens. 2012;21(3):289\u2013300.","journal-title":"Curr Opin Nephrol Hypertens"},{"issue":"2","key":"3054_CR9","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1007\/s00467-011-1772-6","volume":"27","author":"I Grgic","year":"2012","unstructured":"Grgic I, Duffield JS, Humphreys BD. The origin of interstitial myofibroblasts in chronic kidney disease. Pediatr Nephrol. 2012;27(2):183\u201393.","journal-title":"Pediatr Nephrol"},{"issue":"8","key":"3054_CR10","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1038\/nm.3218","volume":"19","author":"VS LeBleu","year":"2013","unstructured":"LeBleu VS, Taduri G, O\u2019Connell J, Teng Y, Cooke VG, Woda C, et al. Origin and function of myofibroblasts in kidney fibrosis. Nat Med. 2013;19(8):1047\u201353.","journal-title":"Nat Med"},{"issue":"3","key":"3054_CR11","doi-asserted-by":"publisher","first-page":"203","DOI":"10.4161\/cam.20377","volume":"6","author":"M Otranto","year":"2012","unstructured":"Otranto M, Sarrazy V, Bonte F, Hinz B, Gabbiani G, Desmouliere A. The role of the myofibroblast in tumor stroma remodeling. Cell Adh Migr. 2012;6(3):203\u201319.","journal-title":"Cell Adh Migr"},{"issue":"1","key":"3054_CR12","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.kint.2022.08.036","volume":"103","author":"N Dwivedi","year":"2023","unstructured":"Dwivedi N, Jamadar A, Mathew S, Fields TA, Rao R. Myofibroblast depletion reduces kidney cyst growth and fibrosis in autosomal dominant polycystic kidney disease. Kidney Int. 2023;103(1):144\u201355.","journal-title":"Kidney Int"},{"issue":"8","key":"3054_CR13","doi-asserted-by":"publisher","first-page":"1697","DOI":"10.1681\/ASN.2020020190","volume":"31","author":"N Dwivedi","year":"2020","unstructured":"Dwivedi N, Tao S, Jamadar A, Sinha S, Howard C, Wallace DP, et al. Epithelial Vasopressin Type-2 Receptors Regulate Myofibroblasts by a YAP-CCN2-Dependent Mechanism in Polycystic Kidney Disease. J Am Soc Nephrol. 2020;31(8):1697\u2013710.","journal-title":"J Am Soc Nephrol"},{"issue":"10","key":"3054_CR14","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1038\/s41419-021-04248-9","volume":"12","author":"A Jamadar","year":"2021","unstructured":"Jamadar A, Suma SM, Mathew S, Fields TA, Wallace DP, Calvet JP, et al. The tyrosine-kinase inhibitor Nintedanib ameliorates autosomal-dominant polycystic kidney disease. Cell Death Dis. 2021;12(10):947.","journal-title":"Cell Death Dis"},{"key":"3054_CR15","first-page":"672225","volume":"2025.08.25","author":"V Remadevi","year":"2025","unstructured":"Remadevi V, Jamadar A, Varghese MM, Gunewardena S, Wallace D, Rao R. Pirfenidone treatment attenuates fibrosis in autosomal dominant polycystic kidney disease. bioRxiv. 2025;2025.08.25:672225.","journal-title":"bioRxiv"},{"issue":"7020","key":"3054_CR16","doi-asserted-by":"publisher","first-page":"1032","DOI":"10.1038\/nature03029","volume":"432","author":"A Kuma","year":"2004","unstructured":"Kuma A, Hatano M, Matsui M, Yamamoto A, Nakaya H, Yoshimori T, et al. The role of autophagy during the early neonatal starvation period. Nature. 2004;432(7020):1032\u20136.","journal-title":"Nature"},{"issue":"1","key":"3054_CR17","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.mam.2011.09.001","volume":"33","author":"AM Cuervo","year":"2012","unstructured":"Cuervo AM, Macian F. Autophagy, nutrition and immunology. Mol Aspects Med. 2012;33(1):2\u201313.","journal-title":"Mol Aspects Med"},{"issue":"9","key":"3054_CR18","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1038\/nrclinonc.2011.71","volume":"8","author":"F Janku","year":"2011","unstructured":"Janku F, McConkey DJ, Hong DS, Kurzrock R. Autophagy as a target for anticancer therapy. Nat Rev Clin Oncol. 2011;8(9):528\u201339.","journal-title":"Nat Rev Clin Oncol"},{"issue":"6","key":"3054_CR19","doi-asserted-by":"publisher","first-page":"e2200221","DOI":"10.1002\/adbi.202200221","volume":"7","author":"K Neikirk","year":"2023","unstructured":"Neikirk K, Vue Z, Katti P, Rodriguez BI, Omer S, Shao J, et al. Systematic Transmission Electron Microscopy-Based Identification and 3D Reconstruction of Cellular Degradation Machinery. Adv Biol (Weinh). 2023;7(6):e2200221.","journal-title":"Adv Biol (Weinh)"},{"issue":"7","key":"3054_CR20","doi-asserted-by":"publisher","first-page":"1958","DOI":"10.1681\/ASN.2015030231","volume":"27","author":"M Chiaravalli","year":"2016","unstructured":"Chiaravalli M, Rowe I, Mannella V, Quilici G, Canu T, Bianchi V, et al. 2-Deoxy-d-Glucose Ameliorates PKD Progression. J Am Soc Nephrol. 2016;27(7):1958\u201369.","journal-title":"J Am Soc Nephrol"},{"issue":"1","key":"3054_CR21","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.semnephrol.2013.11.005","volume":"34","author":"K Ravichandran","year":"2014","unstructured":"Ravichandran K, Edelstein CL. Polycystic kidney disease: a case of suppressed autophagy? Semin Nephrol. 2014;34(1):27\u201333.","journal-title":"Semin Nephrol"},{"issue":"1","key":"3054_CR22","first-page":"158","volume":"26","author":"P Zhu","year":"2017","unstructured":"Zhu P, Sieben CJ, Xu X, Harris PC, Lin X. Autophagy activators suppress cystogenesis in an autosomal dominant polycystic kidney disease model. Hum Mol Genet. 2017;26(1):158\u201372.","journal-title":"Hum Mol Genet"},{"key":"3054_CR23","doi-asserted-by":"publisher","first-page":"102986","DOI":"10.1016\/j.ebiom.2020.102986","volume":"60","author":"EJ Lee","year":"2020","unstructured":"Lee EJ, Ko JY, Oh S, Jun J, Mun H, Lim CJ, et al. Autophagy induction promotes renal cyst growth in polycystic kidney disease. EBioMedicine. 2020;60:102986.","journal-title":"EBioMedicine"},{"issue":"21","key":"3054_CR24","doi-asserted-by":"publisher","first-page":"4297","DOI":"10.4161\/cc.9.21.13817","volume":"9","author":"UE Martinez-Outschoorn","year":"2010","unstructured":"Martinez-Outschoorn UE, Whitaker-Menezes D, Pavlides S, Chiavarina B, Bonuccelli G, Casey T, et al. The autophagic tumor stroma model of cancer or battery-operated tumor growth: A simple solution to the autophagy paradox. Cell Cycle. 2010;9(21):4297\u2013306.","journal-title":"Cell Cycle"},{"key":"3054_CR25","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1007\/978-1-59745-352-3_3","volume":"466","author":"L Grimwood","year":"2009","unstructured":"Grimwood L, Masterson R. Propagation and culture of renal fibroblasts. Methods Mol Biol. 2009;466:25\u201337.","journal-title":"Methods Mol Biol"},{"issue":"15","key":"3054_CR26","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1161\/CIRCULATIONAHA.122.061846","volume":"147","author":"VS Hahn","year":"2023","unstructured":"Hahn VS, Petucci C, Kim MS, Bedi KC Jr., Wang H, Mishra S, et al. Myocardial Metabolomics of Human Heart Failure With Preserved Ejection Fraction. Circulation. 2023;147(15):1147\u201361.","journal-title":"Circulation"},{"issue":"11","key":"3054_CR27","doi-asserted-by":"publisher","first-page":"4257","DOI":"10.1172\/JCI64313","volume":"122","author":"K Hopp","year":"2012","unstructured":"Hopp K, Ward CJ, Hommerding CJ, Nasr SH, Tuan HF, Gainullin VG, et al. Functional polycystin-1 dosage governs autosomal dominant polycystic kidney disease severity. J Clin Invest. 2012;122(11):4257\u201373.","journal-title":"J Clin Invest"},{"issue":"4","key":"3054_CR28","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1007\/s10456-017-9570-9","volume":"20","author":"H Cuervo","year":"2017","unstructured":"Cuervo H, Pereira B, Nadeem T, Lin M, Lee F, Kitajewski J, et al. PDGFRbeta-P2A-CreER(T2) mice: a genetic tool to target pericytes in angiogenesis. Angiogenesis. 2017;20(4):655\u201362.","journal-title":"Angiogenesis"},{"issue":"7","key":"3054_CR29","doi-asserted-by":"publisher","first-page":"e3000410","DOI":"10.1371\/journal.pbio.3000410","volume":"18","author":"N Percie du Sert","year":"2020","unstructured":"Percie du Sert N, Hurst V, Ahluwalia A, Alam S, Avey MT, Baker M, et al. The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. PLoS Biol. 2020;18(7):e3000410.","journal-title":"PLoS Biol"},{"issue":"14","key":"3054_CR30","doi-asserted-by":"publisher","first-page":"7601","DOI":"10.3390\/ijms23147601","volume":"23","author":"A Jamadar","year":"2022","unstructured":"Jamadar A, Dwivedi N, Mathew S, Calvet JP, Thomas SM, Rao R. Vasopressin Receptor Type-2 Mediated Signaling in Renal Cell Carcinoma Stimulates Stromal Fibroblast Activation. Int J Mol Sci. 2022;23(14):7601.","journal-title":"Int J Mol Sci"},{"issue":"6","key":"3054_CR31","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1038\/s41388-019-1059-0","volume":"39","author":"S Sinha","year":"2020","unstructured":"Sinha S, Dwivedi N, Tao S, Jamadar A, Kakade VR, Neil MO, et al. Targeting the vasopressin type-2 receptor for renal cell carcinoma therapy. Oncogene. 2020;39(6):1231\u201345.","journal-title":"Oncogene"},{"issue":"12","key":"3054_CR32","doi-asserted-by":"publisher","first-page":"1943","DOI":"10.1177\/40.12.1280666","volume":"40","author":"DR Abrahamson","year":"1992","unstructured":"Abrahamson DR, St John PL. Loss of laminin epitopes during glomerular basement membrane assembly in developing mouse kidneys. J Histochem Cytochem. 1992;40(12):1943\u201353.","journal-title":"J Histochem Cytochem"},{"key":"3054_CR33","doi-asserted-by":"crossref","unstructured":"Jamadar A, Ward CJ, Remadevi V, Varghese MM, Pabla NS, Gumz ML, et al. Circadian Clock Disruption and Growth of Kidney Cysts in Autosomal Dominant Polycystic Kidney Disease. J Am Soc Nephrol. 2025;36(3):378\u201392.","DOI":"10.1681\/ASN.0000000528"},{"issue":"6","key":"3054_CR34","doi-asserted-by":"publisher","first-page":"F650","DOI":"10.1152\/ajprenal.00516.2014","volume":"308","author":"R Norregaard","year":"2015","unstructured":"Norregaard R, Tao S, Nilsson L, Woodgett JR, Kakade V, Yu AS, et al. Glycogen synthase kinase 3alpha regulates urine concentrating mechanism in mice. Am J Physiol Ren Physiol. 2015;308(6):F650\u201360.","journal-title":"Am J Physiol Ren Physiol"},{"issue":"8","key":"3054_CR35","first-page":"931","volume":"8","author":"SP Singh","year":"2015","unstructured":"Singh SP, Tao S, Fields TA, Webb S, Harris RC, Rao R. Glycogen synthase kinase-3 inhibition attenuates fibroblast activation and development of fibrosis following renal ischemia-reperfusion in mice. Dis Model Mech. 2015;8(8):931\u201340.","journal-title":"Dis Model Mech"},{"issue":"4","key":"3054_CR36","doi-asserted-by":"publisher","first-page":"F553","DOI":"10.1152\/ajprenal.00078.2024","volume":"327","author":"BW Busselman","year":"2024","unstructured":"Busselman BW, Ratnayake I, Terasaki MR, Thakkar VP, Ilyas A, Otterpohl KL, et al. Actin cytoskeleton and associated myosin motors within the renal epithelium. Am J Physiol Ren Physiol. 2024;327(4):F553\u201365.","journal-title":"Am J Physiol Ren Physiol"},{"issue":"21","key":"3054_CR37","doi-asserted-by":"publisher","first-page":"5720","DOI":"10.1093\/emboj\/19.21.5720","volume":"19","author":"Y Kabeya","year":"2000","unstructured":"Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, et al. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 2000;19(21):5720\u20138.","journal-title":"EMBO J"},{"issue":"6","key":"3054_CR38","doi-asserted-by":"publisher","first-page":"542","DOI":"10.4161\/auto.4600","volume":"3","author":"N Mizushima","year":"2007","unstructured":"Mizushima N, Yoshimori T. How to interpret LC3 immunoblotting. Autophagy. 2007;3(6):542\u20135.","journal-title":"Autophagy"},{"issue":"6","key":"3054_CR39","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1080\/15548627.2016.1166317","volume":"12","author":"MJ Livingston","year":"2016","unstructured":"Livingston MJ, Ding HF, Huang S, Hill JA, Yin XM, Dong Z. Persistent activation of autophagy in kidney tubular cells promotes renal interstitial fibrosis during unilateral ureteral obstruction. Autophagy. 2016;12(6):976\u201398.","journal-title":"Autophagy"},{"issue":"3","key":"3054_CR40","doi-asserted-by":"publisher","first-page":"e11021","DOI":"10.15252\/emmm.201911021","volume":"12","author":"EM Buhl","year":"2020","unstructured":"Buhl EM, Djudjaj S, Klinkhammer BM, Ermert K, Puelles VG, Lindenmeyer MT, et al. Dysregulated mesenchymal PDGFR-beta drives kidney fibrosis. EMBO Mol Med. 2020;12(3):e11021.","journal-title":"EMBO Mol Med"},{"issue":"6","key":"3054_CR41","doi-asserted-by":"publisher","first-page":"1392","DOI":"10.1016\/j.kint.2021.01.028","volume":"99","author":"J Arroyo","year":"2021","unstructured":"Arroyo J, Escobar-Zarate D, Wells HH, Constans MM, Thao K, Smith JM, et al. The genetic background significantly impacts the severity of kidney cystic disease in the Pkd1(RC\/RC) mouse model of autosomal dominant polycystic kidney disease. Kidney Int. 2021;99(6):1392\u2013407.","journal-title":"Kidney Int"},{"issue":"2","key":"3054_CR42","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1093\/toxsci\/kfs133","volume":"127","author":"HM Ni","year":"2012","unstructured":"Ni HM, Boggess N, McGill MR, Lebofsky M, Borude P, Apte U, et al. Liver-specific loss of Atg5 causes persistent activation of Nrf2 and protects against acetaminophen-induced liver injury. Toxicol Sci. 2012;127(2):438\u201350.","journal-title":"Toxicol Sci"},{"issue":"5","key":"3054_CR43","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1016\/j.kint.2018.06.008","volume":"94","author":"A Kraus","year":"2018","unstructured":"Kraus A, Peters DJM, Klanke B, Weidemann A, Willam C, Schley G, et al. HIF-1alpha promotes cyst progression in a mouse model of autosomal dominant polycystic kidney disease. Kidney Int. 2018;94(5):887\u201399.","journal-title":"Kidney Int"},{"issue":"2","key":"3054_CR44","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1016\/j.bbrc.2014.10.076","volume":"454","author":"J Deng","year":"2014","unstructured":"Deng J, Huang Q, Wang Y, Shen P, Guan F, Li J, et al. Hypoxia-inducible factor-1alpha regulates autophagy to activate hepatic stellate cells. Biochem Biophys Res Commun. 2014;454(2):328\u201334.","journal-title":"Biochem Biophys Res Commun"},{"issue":"1","key":"3054_CR45","doi-asserted-by":"publisher","first-page":"112175","DOI":"10.1016\/j.yexcr.2020.112175","volume":"395","author":"M Deng","year":"2020","unstructured":"Deng M, Zhang W, Yuan L, Tan J, Chen Z. HIF-1a regulates hypoxia-induced autophagy via translocation of ANKRD37 in colon cancer. Exp Cell Res. 2020;395(1):112175.","journal-title":"Exp Cell Res"},{"issue":"10","key":"3054_CR46","doi-asserted-by":"publisher","first-page":"e46571","DOI":"10.1371\/journal.pone.0046571","volume":"7","author":"CJ De Saedeleer","year":"2012","unstructured":"De Saedeleer CJ, Copetti T, Porporato PE, Verrax J, Feron O, Sonveaux P. Lactate activates HIF-1 in oxidative but not in Warburg-phenotype human tumor cells. PLoS ONE. 2012;7(10):e46571.","journal-title":"PLoS ONE"},{"issue":"7","key":"3054_CR47","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1016\/j.bcp.2010.06.018","volume":"80","author":"K Lee","year":"2010","unstructured":"Lee K, Kang JE, Park SK, Jin Y, Chung KS, Kim HM, et al. LW6, a novel HIF-1 inhibitor, promotes proteasomal degradation of HIF-1alpha via upregulation of VHL in a colon cancer cell line. Biochem Pharmacol. 2010;80(7):982\u20139.","journal-title":"Biochem Pharmacol"},{"key":"3054_CR48","doi-asserted-by":"publisher","first-page":"100973","DOI":"10.1016\/j.mam.2021.100973","volume":"82","author":"H Qian","year":"2021","unstructured":"Qian H, Chao X, Williams J, Fulte S, Li T, Yang L, et al. Autophagy in liver diseases: A review. Mol Aspects Med. 2021;82:100973.","journal-title":"Mol Aspects Med"},{"issue":"9","key":"3054_CR49","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1038\/s41581-020-0309-2","volume":"16","author":"C Tang","year":"2020","unstructured":"Tang C, Livingston MJ, Liu Z, Dong Z. Autophagy in kidney homeostasis and disease. Nat Rev Nephrol. 2020;16(9):489\u2013508.","journal-title":"Nat Rev Nephrol"},{"key":"3054_CR50","doi-asserted-by":"publisher","first-page":"109760","DOI":"10.1016\/j.cellsig.2020.109760","volume":"75","author":"DJ Atwood","year":"2020","unstructured":"Atwood DJ, Brown CN, Holditch SJ, Pokhrel D, Thorburn A, Hopp K, et al. The effect of trehalose on autophagy-related proteins and cyst growth in a hypomorphic Pkd1 mouse model of autosomal dominant polycystic kidney disease. Cell Signal. 2020;75:109760.","journal-title":"Cell Signal"},{"key":"3054_CR51","doi-asserted-by":"crossref","unstructured":"Chou LF, Cheng YL, Hsieh CY, Lin CY, Yang HY, Chen YC, et al. Effect of Trehalose Supplementation on Autophagy and Cystogenesis in a Mouse Model of Polycystic Kidney Disease. Nutrients. 2018;11(1):42\u201358.","DOI":"10.3390\/nu11010042"},{"issue":"3","key":"3054_CR52","doi-asserted-by":"publisher","first-page":"e1696","DOI":"10.1038\/cddis.2015.36","volume":"6","author":"S Ghavami","year":"2015","unstructured":"Ghavami S, Cunnington RH, Gupta S, Yeganeh B, Filomeno KL, Freed DH, et al. Autophagy is a regulator of TGF-beta1-induced fibrogenesis in primary human atrial myofibroblasts. Cell Death Dis. 2015;6(3):e1696.","journal-title":"Cell Death Dis"},{"issue":"48","key":"3054_CR53","doi-asserted-by":"publisher","first-page":"78516","DOI":"10.18632\/oncotarget.12392","volume":"7","author":"SS Gupta","year":"2016","unstructured":"Gupta SS, Zeglinski MR, Rattan SG, Landry NM, Ghavami S, Wigle JT, et al. Inhibition of autophagy inhibits the conversion of cardiac fibroblasts to cardiac myofibroblasts. Oncotarget. 2016;7(48):78516\u201331.","journal-title":"Oncotarget"},{"issue":"13\u201314","key":"3054_CR54","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1101\/gad.345629.120","volume":"35","author":"JA Rudnick","year":"2021","unstructured":"Rudnick JA, Monkkonen T, Mar FA, Barnes JM, Starobinets H, Goldsmith J, et al. Autophagy in stromal fibroblasts promotes tumor desmoplasia and mammary tumorigenesis. Genes Dev. 2021;35(13\u201314):963\u201375.","journal-title":"Genes Dev"},{"issue":"1","key":"3054_CR55","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1038\/s41598-020-79789-8","volume":"11","author":"ML Tan","year":"2021","unstructured":"Tan ML, Parkinson EK, Yap LF, Paterson IC. Autophagy is deregulated in cancer-associated fibroblasts from oral cancer and is stimulated during the induction of fibroblast senescence by TGF-beta1. Sci Rep. 2021;11(1):584.","journal-title":"Sci Rep"},{"issue":"6","key":"3054_CR56","doi-asserted-by":"publisher","first-page":"1314","DOI":"10.1080\/15548627.2023.2300913","volume":"20","author":"X Zhang","year":"2024","unstructured":"Zhang X, Lao M, Yang H, Sun K, Dong Y, He L, et al. Targeting cancer-associated fibroblast autophagy renders pancreatic cancer eradicable with immunochemotherapy by inhibiting adaptive immune resistance. Autophagy. 2024;20(6):1314\u201334.","journal-title":"Autophagy"},{"key":"3054_CR57","doi-asserted-by":"publisher","first-page":"109648","DOI":"10.1016\/j.cellsig.2020.109648","volume":"72","author":"C Formica","year":"2020","unstructured":"Formica C, Peters DJM. Molecular pathways involved in injury-repair and ADPKD progression. Cell Signal. 2020;72:109648.","journal-title":"Cell Signal"},{"issue":"5","key":"3054_CR58","doi-asserted-by":"publisher","first-page":"F693","DOI":"10.1152\/ajprenal.00545.2020","volume":"320","author":"EA Nigro","year":"2021","unstructured":"Nigro EA, Boletta A. Role of the polycystins as mechanosensors of extracellular stiffness. Am J Physiol Ren Physiol. 2021;320(5):F693\u2013705.","journal-title":"Am J Physiol Ren Physiol"},{"key":"3054_CR59","doi-asserted-by":"publisher","first-page":"109646","DOI":"10.1016\/j.cellsig.2020.109646","volume":"72","author":"Y Zhang","year":"2020","unstructured":"Zhang Y, Reif G, Wallace DP. Extracellular matrix, integrins, and focal adhesion signaling in polycystic kidney disease. Cell Signal. 2020;72:109646.","journal-title":"Cell Signal"},{"issue":"10","key":"3054_CR60","doi-asserted-by":"publisher","first-page":"1809","DOI":"10.1681\/ASN.2011010084","volume":"22","author":"A Karihaloo","year":"2011","unstructured":"Karihaloo A, Koraishy F, Huen SC, Lee Y, Merrick D, Caplan MJ, et al. Macrophages promote cyst growth in polycystic kidney disease. J Am Soc Nephrol. 2011;22(10):1809\u201314.","journal-title":"J Am Soc Nephrol"},{"issue":"6","key":"3054_CR61","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1016\/j.kint.2018.06.025","volume":"94","author":"EK Kleczko","year":"2018","unstructured":"Kleczko EK, Marsh KH, Tyler LC, Furgeson SB, Bullock BL, Altmann CJ, et al. CD8(+) T cells modulate autosomal dominant polycystic kidney disease progression. Kidney Int. 2018;94(6):1127\u201340.","journal-title":"Kidney Int"},{"issue":"5","key":"3054_CR62","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1038\/ki.2012.446","volume":"83","author":"KI Swenson-Fields","year":"2013","unstructured":"Swenson-Fields KI, Vivian CJ, Salah SM, Peda JD, Davis BM, van Rooijen N, et al. Macrophages promote polycystic kidney disease progression. Kidney Int. 2013;83(5):855\u201364.","journal-title":"Kidney Int"},{"issue":"1","key":"3054_CR63","doi-asserted-by":"publisher","first-page":"e13951","DOI":"10.14814\/phy2.13951","volume":"7","author":"KA Zimmerman","year":"2019","unstructured":"Zimmerman KA, Gonzalez NM, Chumley P, Chacana T, Harrington LE, Yoder BK, et al. Urinary T cells correlate with rate of renal function loss in autosomal dominant polycystic kidney disease. Physiol Rep. 2019;7(1):e13951.","journal-title":"Physiol Rep"},{"issue":"10","key":"3054_CR64","doi-asserted-by":"publisher","first-page":"1841","DOI":"10.1681\/ASN.2018080810","volume":"30","author":"KA Zimmerman","year":"2019","unstructured":"Zimmerman KA, Song CJ, Li Z, Lever JM, Crossman DK, Rains A, et al. Tissue-Resident Macrophages Promote Renal Cystic Disease. J Am Soc Nephrol. 2019;30(10):1841\u201356.","journal-title":"J Am Soc Nephrol"},{"issue":"24","key":"3054_CR65","doi-asserted-by":"publisher","first-page":"4228","DOI":"10.1093\/hmg\/ddac175","volume":"31","author":"CL Hsieh","year":"2022","unstructured":"Hsieh CL, Jerman SJ, Sun Z. Non-cell-autonomous activation of hedgehog signaling contributes to disease progression in a mouse model of renal cystic ciliopathy. Hum Mol Genet. 2022;31(24):4228\u201340.","journal-title":"Hum Mol Genet"},{"key":"3054_CR66","doi-asserted-by":"crossref","unstructured":"Lichner Z, Ding M, Khare T, Dan Q, Benitez R, Praszner M, et al. Myocardin-Related Transcription Factor Mediates Epithelial Fibrogenesis in Polycystic Kidney Disease. Cells. 2024;13(11):984\u20131010.","DOI":"10.3390\/cells13110984"},{"key":"3054_CR67","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1038\/s42003-018-0200-x","volume":"1","author":"C Podrini","year":"2018","unstructured":"Podrini C, Rowe I, Pagliarini R, Costa ASH, Chiaravalli M, Di Meo I, et al. Dissection of metabolic reprogramming in polycystic kidney disease reveals coordinated rewiring of bioenergetic pathways. Commun Biol. 2018;1:194.","journal-title":"Commun Biol"},{"issue":"4","key":"3054_CR68","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1038\/nm.3092","volume":"19","author":"I Rowe","year":"2013","unstructured":"Rowe I, Chiaravalli M, Mannella V, Ulisse V, Quilici G, Pema M, et al. Defective glucose metabolism in polycystic kidney disease identifies a new therapeutic strategy. Nat Med. 2013;19(4):488\u201393.","journal-title":"Nat Med"},{"issue":"22","key":"3054_CR69","doi-asserted-by":"publisher","first-page":"eadg4993","DOI":"10.1126\/sciadv.adg4993","volume":"9","author":"M Jia","year":"2023","unstructured":"Jia M, Yue X, Sun W, Zhou Q, Chang C, Gong W, et al. ULK1-mediated metabolic reprogramming regulates Vps34 lipid kinase activity by its lactylation. Sci Adv. 2023;9(22):eadg4993.","journal-title":"Sci Adv"},{"issue":"1","key":"3054_CR70","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1007\/s12079-019-00534-6","volume":"14","author":"BC Su","year":"2020","unstructured":"Su BC, Hsu PL, Mo FE. CCN1 triggers adaptive autophagy in cardiomyocytes to curb its apoptotic activities. J Cell Commun Signal. 2020;14(1):93\u2013100.","journal-title":"J Cell Commun Signal"},{"issue":"5","key":"3054_CR71","doi-asserted-by":"publisher","first-page":"213","DOI":"10.31083\/ph.2020.0336","volume":"75","author":"Y Ni","year":"2020","unstructured":"Ni Y, Zhang H, Li Z, Li Z. Connective tissue growth factor (CCN2) inhibits TNF-alpha-induced apoptosis by enhancing autophagy through the Akt and Erk pathways in osteoblasts. Pharmazie. 2020;75(5):213\u20137.","journal-title":"Pharmazie"},{"issue":"5","key":"3054_CR72","doi-asserted-by":"publisher","first-page":"F1235","DOI":"10.1152\/ajprenal.00348.2010","volume":"300","author":"F Belibi","year":"2011","unstructured":"Belibi F, Zafar I, Ravichandran K, Segvic AB, Jani A, Ljubanovic DG, et al. Hypoxia-inducible factor-1alpha (HIF-1alpha) and autophagy in polycystic kidney disease (PKD). Am J Physiol Ren Physiol. 2011;300(5):F1235\u201343.","journal-title":"Am J Physiol Ren Physiol"},{"issue":"3","key":"3054_CR73","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1681\/ASN.2013030209","volume":"25","author":"B Buchholz","year":"2014","unstructured":"Buchholz B, Schley G, Faria D, Kroening S, Willam C, Schreiber R, et al. Hypoxia-inducible factor-1alpha causes renal cyst expansion through calcium-activated chloride secretion. J Am Soc Nephrol. 2014;25(3):465\u201374.","journal-title":"J Am Soc Nephrol"},{"issue":"6","key":"3054_CR74","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1016\/j.semnephrol.2019.10.009","volume":"39","author":"M Theodorakopoulou","year":"2019","unstructured":"Theodorakopoulou M, Raptis V, Loutradis C, Sarafidis P. Hypoxia and Endothelial Dysfunction in Autosomal-Dominant Polycystic Kidney Disease. Semin Nephrol. 2019;39(6):599\u2013612.","journal-title":"Semin Nephrol"},{"issue":"4","key":"3054_CR75","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1172\/JCI114280","volume":"84","author":"KU Eckardt","year":"1989","unstructured":"Eckardt KU, Mollmann M, Neumann R, Brunkhorst R, Burger HU, Lonnemann G, et al. Erythropoietin in polycystic kidneys. J Clin Invest. 1989;84(4):1160\u20136.","journal-title":"J Clin Invest"},{"issue":"14","key":"3054_CR76","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.1056\/NEJMcp0804458","volume":"359","author":"JJ Grantham","year":"2008","unstructured":"Grantham JJ. Clinical practice. Autosomal dominant polycystic kidney disease. N Engl J Med. 2008;359(14):1477\u201385.","journal-title":"N Engl J Med"},{"key":"3054_CR77","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.1100\/tsw.2007.274","volume":"7","author":"S Ibrahim","year":"2007","unstructured":"Ibrahim S. Increased apoptosis and proliferative capacity are early events in cyst formation in autosomal-dominant, polycystic kidney disease. ScientificWorldJournal. 2007;7:1757\u201367.","journal-title":"ScientificWorldJournal"},{"issue":"10","key":"3054_CR78","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1016\/j.bbadis.2011.06.012","volume":"1812","author":"J Norman","year":"2011","unstructured":"Norman J. Fibrosis and progression of autosomal dominant polycystic kidney disease (ADPKD). Biochim Biophys Acta. 2011;1812(10):1327\u201336.","journal-title":"Biochim Biophys Acta"},{"issue":"10","key":"3054_CR79","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1038\/s41581-019-0182-z","volume":"15","author":"J Schodel","year":"2019","unstructured":"Schodel J, Ratcliffe PJ. Mechanisms of hypoxia signalling: new implications for nephrology. Nat Rev Nephrol. 2019;15(10):641\u201359.","journal-title":"Nat Rev Nephrol"},{"key":"3054_CR80","doi-asserted-by":"publisher","first-page":"175154","DOI":"10.1016\/j.ejphar.2022.175154","volume":"930","author":"H Xu","year":"2022","unstructured":"Xu H, Chen Y, Li Z, Zhang H, Liu J, Han J. The hypoxia-inducible factor 1 inhibitor LW6 mediates the HIF-1alpha\/PD-L1 axis and suppresses tumor growth of hepatocellular carcinoma in vitro and in vivo. Eur J Pharmacol. 2022;930:175154.","journal-title":"Eur J Pharmacol"},{"issue":"5","key":"3054_CR81","doi-asserted-by":"publisher","first-page":"1959","DOI":"10.3892\/etm.2015.2763","volume":"10","author":"T Eleftheriadis","year":"2015","unstructured":"Eleftheriadis T, Pissas G, Antoniadi G, Liakopoulos V, Stefanidis I. Malate dehydrogenase-2 inhibitor LW6 promotes metabolic adaptations and reduces proliferation and apoptosis in activated human T-cells. Exp Ther Med. 2015;10(5):1959\u201366.","journal-title":"Exp Ther Med"},{"issue":"3","key":"3054_CR82","doi-asserted-by":"publisher","first-page":"3462","DOI":"10.3892\/mmr.2015.3862","volume":"12","author":"M Sato","year":"2015","unstructured":"Sato M, Hirose K, Kashiwakura I, Aoki M, Kawaguchi H, Hatayama Y, et al. LW6, a hypoxia-inducible factor 1 inhibitor, selectively induces apoptosis in hypoxic cells through depolarization of mitochondria in A549 human lung cancer cells. Mol Med Rep. 2015;12(3):3462\u20138.","journal-title":"Mol Med Rep"},{"issue":"7","key":"3054_CR83","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1038\/cdd.2009.16","volume":"16","author":"J Zhang","year":"2009","unstructured":"Zhang J, Ney PA. Role of BNIP3 and NIX in cell death, autophagy, and mitophagy. Cell Death Differ. 2009;16(7):939\u201346.","journal-title":"Cell Death Differ"}],"container-title":["Cell Communication and Signaling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12964-026-03054-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-026-03054-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-026-03054-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:02:16Z","timestamp":1790946136000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12964-026-03054-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,9]]},"references-count":83,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["3054"],"URL":"https:\/\/doi.org\/10.1186\/s12964-026-03054-0","relation":{},"ISSN":["1478-811X"],"issn-type":[{"value":"1478-811X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,9]]},"assertion":[{"value":"8 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All animal experiments received approval from the Institutional Animal Care and Use Committee of the University of Kansas.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"526"}}