{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T14:50:44Z","timestamp":1780325444320,"version":"3.54.1"},"reference-count":110,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T00:00:00Z","timestamp":1695859200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Autosomal-Dominant Polycystic Kidney Disease (ADPKD) is a monogenic disorder initiated by mutations in either PKD1 or PKD2 genes, responsible for encoding polycystin 1 and polycystin 2, respectively. These proteins are primarily located within the primary cilia. The disease follows an inexorable progression, leading most patients to severe renal failure around the age of 50, and extra-renal complications are frequent. A cure for ADPKD remains elusive, but some measures can be employed to manage symptoms and slow cyst growth. Tolvaptan, a vasopressin V2 receptor antagonist, is the only drug that has been proven to attenuate ADPKD progression. Recently, autophagy, a cellular recycling system that facilitates the breakdown and reuse of aged or damaged cellular components, has emerged as a potential contributor to the pathogenesis of ADPKD. However, the precise role of autophagy in ADPKD remains a subject of investigation, displaying a potentially twofold impact. On the one hand, impaired autophagy may promote cyst formation by inducing apoptosis, while on the other hand, excessive autophagy may lead to fibrosis through epithelial to mesenchymal transition. Promising results of autophagy inducers have been observed in preclinical studies. Clinical trials are warranted to thoroughly assess the long-term safety and efficacy of a combination of autophagy inducers with metabolic and\/or aquaferetic drugs. This research aims to shed light on the complex involvement of autophagy in ADPKD, explore the regulation of autophagy in disease progression, and highlight the potential of combination therapies as a promising avenue for future investigations.<\/jats:p>","DOI":"10.3390\/ijms241914666","type":"journal-article","created":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T01:42:12Z","timestamp":1695865332000},"page":"14666","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Autosomal Dominant Polycystic Kidney Disease: Is There a Role for Autophagy?"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6060-965X","authenticated-orcid":false,"given":"Claudio","family":"Ponticelli","sequence":"first","affiliation":[{"name":"Independent Researcher, via Amp\u00e8re 126, 20131 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Moroni","sequence":"additional","affiliation":[{"name":"Nephrology and Dialysis Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9254-618X","authenticated-orcid":false,"given":"Francesco","family":"Reggiani","sequence":"additional","affiliation":[{"name":"Nephrology and Dialysis Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Milan, Italy"},{"name":"Department of Biomedical Sciences, Humanitas University, 20090 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1056\/NEJM199307293290508","article-title":"Autosomal Dominant Polycystic Kidney Disease","volume":"329","author":"Gabow","year":"1993","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/ng0695-151","article-title":"The Polycystic Kidney Disease 1 (PKD1) Gene Encodes a Novel Protein with Multiple Cell Recognition Domains","volume":"10","author":"Hughes","year":"1995","journal-title":"Nat. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1093\/hmg\/4.4.575","article-title":"Analysis of the Genomic Sequence for the Autosomal Dominant Polycystic Kidney Disease (PKD1) Gene Predicts the Presence of a Leucine-Rich Repeat. The American PKD1 Consortium (APKD1 Consortium)","volume":"4","author":"Burn","year":"1995","journal-title":"Hum. Mol. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1053\/j.ajkd.2017.01.046","article-title":"PKD2-Related Autosomal Dominant Polycystic Kidney Disease: Prevalence, Clinical Presentation, Mutation Spectrum, and Prognosis","volume":"70","author":"Renaudineau","year":"2017","journal-title":"Am. J. Kidney Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1146\/annurev.med.60.101707.125712","article-title":"Polycystic Kidney Disease","volume":"60","author":"Harris","year":"2009","journal-title":"Annu. Rev. Med."},{"key":"ref_6","unstructured":"Li, X. (2015). Polycystic Kidney Disease, Codon Publications."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"F693","DOI":"10.1152\/ajprenal.00545.2020","article-title":"Role of the Polycystins as Mechanosensors of Extracellular Stiffness","volume":"320","author":"Nigro","year":"2021","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-018-37186-2","article-title":"Occurrence of the Potent Mutagens 2- Nitrobenzanthrone and 3-Nitrobenzanthrone in Fine Airborne Particles","volume":"9","author":"Santos","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1172\/JCI5111","article-title":"Polycystin-1, the PKD1 Gene Product, Is in a Complex Containing E-Cadherin and the Catenins","volume":"104","author":"Huan","year":"1999","journal-title":"J. Clin. Investig."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"146313","DOI":"10.1016\/j.gene.2022.146313","article-title":"Polycystin-2 (TRPP2): Ion Channel Properties and Regulation","volume":"827","author":"Cantero","year":"2022","journal-title":"Gene"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"eaat9819","DOI":"10.1126\/science.aat9819","article-title":"Structure of the Human PKD1-PKD2 Complex","volume":"361","author":"Su","year":"2018","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"790","DOI":"10.2215\/CJN.02320220","article-title":"Insights into Autosomal Dominant Polycystic Kidney Disease from Genetic Studies","volume":"16","author":"Lanktree","year":"2021","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1091\/mbc.e03-05-0296","article-title":"A Polycystin-1 Multiprotein Complex Is Disrupted in Polycystic Kidney Disease Cells","volume":"15","author":"Roitbak","year":"2004","journal-title":"Mol. Biol. Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2508","DOI":"10.1097\/01.ASN.0000029587.47950.25","article-title":"The Polycystic Kidney Disease Proteins, Polycystin-1, Polycystin-2, Polaris, and Cystin, Are Co-Localized in Renal Cilia","volume":"13","author":"Yoder","year":"2002","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.cub.2019.01.054","article-title":"Tulp3 Is a Ciliary Trafficking Gene That Regulates Polycystic Kidney Disease","volume":"29","author":"Liem","year":"2019","journal-title":"Curr. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/ki.2009.128","article-title":"Autosomal Dominant Polycystic Kidney Disease: The Last 3 Years","volume":"76","author":"Torres","year":"2009","journal-title":"Kidney Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1097\/MNH.0b013e3283621510","article-title":"Osmoregulation, Vasopressin, and cAMP Signaling in Autosomal Dominant Polycystic Kidney Disease","volume":"22","author":"Devuyst","year":"2013","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1681\/ASN.2006111218","article-title":"Identification of a Forskolin-like Molecule in Human Renal Cysts","volume":"18","author":"Putnam","year":"2007","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1007\/s00467-018-4004-5","article-title":"Oxidative Stress in Autosomal Dominant Polycystic Kidney Disease: Player and\/or Early Predictor for Disease Progression?","volume":"34","author":"Andries","year":"2019","journal-title":"Pediatr. Nephrol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.2215\/CJN.05850518","article-title":"Vascular Dysfunction, Oxidative Stress, and Inflammation in Autosomal Dominant Polycystic Kidney Disease","volume":"13","author":"Nowak","year":"2018","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1016\/j.ekir.2021.04.023","article-title":"Chronic Inflammation in Chronic Kidney Disease Progression: Role of Nrf2","volume":"6","author":"Stenvinkel","year":"2021","journal-title":"Kidney Int. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"109495","DOI":"10.1016\/j.cellsig.2019.109495","article-title":"Metabolic Reprogramming and the Role of Mitochondria in Polycystic Kidney Disease","volume":"67","author":"Podrini","year":"2020","journal-title":"Cell. Signal."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"740087","DOI":"10.3389\/fmed.2021.740087","article-title":"Metabolic Reprogramming and Reconstruction: Integration of Experimental and Computational Studies to Set the Path Forward in ADPKD","volume":"8","author":"Pagliarini","year":"2021","journal-title":"Front. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1038\/nm.3092","article-title":"Defective Glucose Metabolism in Polycystic Kidney Disease Identifies a New Therapeutic Strategy","volume":"19","author":"Rowe","year":"2013","journal-title":"Nat. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S1471-4914(01)01953-0","article-title":"A \u201cTwo-Hit\u201d Model of Cystogenesis in Autosomal Dominant Polycystic Kidney Disease?","volume":"7","author":"Pei","year":"2001","journal-title":"Trends Mol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/S0092-8674(00)81793-6","article-title":"The Molecular Basis of Focal Cyst Formation in Human Autosomal Dominant Polycystic Kidney Disease Type I","volume":"87","author":"Qian","year":"1996","journal-title":"Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/S1097-2765(00)80135-5","article-title":"Somatic Mutation in Individual Liver Cysts Supports a Two-Hit Model of Cystogenesis in Autosomal Dominant Polycystic Kidney Disease","volume":"2","author":"Watnick","year":"1998","journal-title":"Mol. Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1038\/nm1675","article-title":"A Critical Developmental Switch Defines the Kinetics of Kidney Cyst Formation after Loss of Pkd1","volume":"13","author":"Piontek","year":"2007","journal-title":"Nat. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3188","DOI":"10.1093\/hmg\/ddm299","article-title":"Kidney-Specific Inactivation of the Pkd1 Gene Induces Rapid Cyst Formation in Developing Kidneys and a Slow Onset of Disease in Adult Mice","volume":"16","author":"Leonhard","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.1093\/hmg\/ddp147","article-title":"Renal Injury Is a Third Hit Promoting Rapid Development of Adult Polycystic Kidney Disease","volume":"18","author":"Takakura","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1053\/j.ackd.2010.01.001","article-title":"Hypertension in Autosomal Dominant Polycystic Kidney Disease","volume":"17","author":"Chapman","year":"2010","journal-title":"Adv. Chronic Kidney Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.2215\/CJN.14691218","article-title":"Presymptomatic Screening for Intracranial Aneurysms in Patients with Autosomal Dominant Polycystic Kidney Disease","volume":"14","author":"Sanchis","year":"2019","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_33","first-page":"69","article-title":"Polycystic Kidney Disease: Inheritance, Pathophysiology, Prognosis, and Treatment","volume":"3","author":"Halvorson","year":"2010","journal-title":"Int. J. Nephrol. Renovasc. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1093\/ndt\/gft437","article-title":"Extra-Renal Manifestations of Autosomal Dominant Polycystic Kidney Disease (ADPKD): Considerations for Routine Screening and Management","volume":"29","author":"Luciano","year":"2014","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.2215\/CJN.03960318","article-title":"Recent Advances in the Management of Autosomal Dominant Polycystic Kidney Disease","volume":"13","author":"Chebib","year":"2018","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"908","DOI":"10.2215\/CJN.16871020","article-title":"Overweight and Obesity and Progression of ADPKD","volume":"16","author":"Nowak","year":"2021","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.kint.2016.10.018","article-title":"Dietary Salt Restriction Is Beneficial to the Management of Autosomal Dominant Polycystic Kidney Disease","volume":"91","author":"Torres","year":"2017","journal-title":"Kidney Int."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.2215\/CJN.00790209","article-title":"A Case for Water in the Treatment of Polycystic Kidney Disease","volume":"4","author":"Torres","year":"2009","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1056\/NEJMoa1402685","article-title":"Blood Pressure in Early Autosomal Dominant Polycystic Kidney Disease","volume":"371","author":"Schrier","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2267","DOI":"10.1056\/NEJMoa1402686","article-title":"Angiotensin Blockade in Late Autosomal Dominant Polycystic Kidney Disease","volume":"371","author":"Torres","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1016\/j.kint.2020.05.056","article-title":"Hyperuricemia as a Trigger of Immune Response in Hypertension and Chronic Kidney Disease","volume":"98","author":"Ponticelli","year":"2020","journal-title":"Kidney Int."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"228","DOI":"10.2174\/1573402116666200817113125","article-title":"Serum Uric Acid and Progression of Autosomal Dominant Polycystic Kidney Disease: Results from the HALT PKD Trials","volume":"17","author":"Brosnahan","year":"2021","journal-title":"Curr. Hypertens. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1007\/s10157-020-01928-2","article-title":"Cyst Infection in Autosomal Dominant Polycystic Kidney Disease: Our Experience at Toranomon Hospital and Future Issues","volume":"24","author":"Suwabe","year":"2020","journal-title":"Clin. Exp. Nephrol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.1056\/NEJMoa1205511","article-title":"Tolvaptan in Patients with Autosomal Dominant Polycystic Kidney Disease","volume":"367","author":"Torres","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1093\/ndt\/gfx043","article-title":"TEMPO 4:4 Trial Investigators Multicenter, Open-Label, Extension Trial to Evaluate the Long-Term Efficacy and Safety of Early versus Delayed Treatment with Tolvaptan in Autosomal Dominant Polycystic Kidney Disease: The TEMPO 4:4 Trial","volume":"33","author":"Torres","year":"2018","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1056\/NEJMoa1710030","article-title":"Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease","volume":"377","author":"Torres","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1093\/ndt\/gfv456","article-title":"Recommendations for the Use of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease: A Position Statement on Behalf of the ERA-EDTA Working Groups on Inherited Kidney Disorders and European Renal Best Practice","volume":"31","author":"Gansevoort","year":"2016","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3532","DOI":"10.1093\/ndt\/gfs152","article-title":"Somatostatin Analog Therapy for Severe Polycystic Liver Disease: Results after 2 Years","volume":"27","author":"Hogan","year":"2012","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1016\/S0140-6736(13)61407-5","article-title":"Effect of Longacting Somatostatin Analogue on Kidney and Cyst Growth in Autosomal Dominant Polycystic Kidney Disease (ALADIN): A Randomised, Placebo-Controlled, Multicentre Trial","volume":"382","author":"Caroli","year":"2013","journal-title":"Lancet"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Perico, N., Ruggenenti, P., Perna, A., Caroli, A., Trillini, M., Sironi, S., Pisani, A., Riccio, E., Imbriaco, M., and Dugo, M. (2019). Octreotide-LAR in Later-Stage Autosomal Dominant Polycystic Kidney Disease (ALADIN 2): A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial. PLoS Med., 16.","DOI":"10.1371\/journal.pmed.1002777"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"223","DOI":"10.2215\/CJN.0000000000000049","article-title":"Effects of Octreotide-Long-Acting Release Added-on Tolvaptan in Patients with Autosomal Dominant Polycystic Kidney Disease: Pilot, Randomized, Placebo-Controlled, Cross-Over Trial","volume":"18","author":"Trillini","year":"2023","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.1681\/ASN.2015030231","article-title":"2-Deoxy-d-Glucose Ameliorates PKD Progression","volume":"27","author":"Chiaravalli","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1038\/s41588-021-00963-3","article-title":"Reversing Polycystic Kidney Disease","volume":"53","author":"Boletta","year":"2021","journal-title":"Nat. Genet."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1007\/s40620-017-0395-9","article-title":"Defective Glycolysis and the Use of 2-Deoxy-d-Glucose in Polycystic Kidney Disease: From Animal Models to Humans","volume":"30","author":"Magistroni","year":"2017","journal-title":"J. Nephrol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2861","DOI":"10.1101\/gad.1599207","article-title":"Autophagy: Process and Function","volume":"21","author":"Mizushima","year":"2007","journal-title":"Genes Dev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1755-8417-2-6","article-title":"Emerging Evidence of a Link between the Polycystins and the mTOR Pathways","volume":"2","author":"Boletta","year":"2009","journal-title":"Pathogenetics"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/ncb2152","article-title":"AMPK and mTOR Regulate Autophagy through Direct Phosphorylation of Ulk1","volume":"13","author":"Kim","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1038\/ncb2708","article-title":"mTOR Inhibits Autophagy by Controlling ULK1 Ubiquitylation, Self-Association and Function through AMBRA1 and TRAF6","volume":"15","author":"Nazio","year":"2013","journal-title":"Nat. Cell. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Holczer, M., Hajd\u00fa, B., L\u0151rincz, T., Szarka, A., B\u00e1nhegyi, G., and Kapuy, O. (2019). A Double Negative Feedback Loop between mTORC1 and AMPK Kinases Guarantees Precise Autophagy Induction upon Cellular Stress. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20225543"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"jcs259393","DOI":"10.1242\/jcs.259393","article-title":"Selective Microautophagy of Proteasomes Is Initiated by ESCRT-0 and Is Promoted by Proteasome Ubiquitylation","volume":"135","author":"Li","year":"2022","journal-title":"J. Cell. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1007\/s00018-011-0865-5","article-title":"Microautophagy: Lesser-Known Self-Eating","volume":"69","author":"Li","year":"2012","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1080\/15548627.2020.1717206","article-title":"ESCRTing Endoplasmic Reticulum to Microautophagic Degradation","volume":"16","author":"Schuck","year":"2020","journal-title":"Autophagy"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/s41580-018-0001-6","article-title":"The Coming of Age of Chaperone-Mediated Autophagy","volume":"19","author":"Kaushik","year":"2018","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.semcancer.2019.03.002","article-title":"Ferroptosis Is a Type of Autophagy-Dependent Cell Death","volume":"66","author":"Zhou","year":"2020","journal-title":"Semin. Cancer Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2384","DOI":"10.1080\/15548627.2020.1826716","article-title":"Loss of PKD1\/Polycystin-1 Impairs Lysosomal Activity in a CAPN (Calpain)-Dependent Manner","volume":"17","author":"Peintner","year":"2021","journal-title":"Autophagy"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1080\/15548627.2020.1782035","article-title":"PKD2\/Polycystin-2 Induces Autophagy by Forming a Complex with BECN1","volume":"17","author":"Vergara","year":"2021","journal-title":"Autophagy"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"109518","DOI":"10.1016\/j.cellsig.2019.109518","article-title":"Apoptosis and Autophagy in Polycystic Kidney Disease (PKD)","volume":"68","author":"Nowak","year":"2020","journal-title":"Cell. Signal."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.yjmcc.2018.03.002","article-title":"Polycystin-2-Dependent Control of Cardiomyocyte Autophagy","volume":"118","author":"Criollo","year":"2018","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1053\/j.ajkd.2015.05.021","article-title":"Autophagy and the Kidney: Implications for Ischemia-Reperfusion Injury and Therapy","volume":"66","author":"Decuypere","year":"2015","journal-title":"Am. J. Kidney Dis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/j.biopha.2017.07.165","article-title":"Steviol Stabilizes Polycystin 1 Expression and Promotes Lysosomal Degradation of CFTR and \u03b2-Catenin Proteins in Renal Epithelial Cells","volume":"94","author":"Yuajit","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/nature12639","article-title":"Functional Interaction between Autophagy and Ciliogenesis","volume":"502","author":"Pampliega","year":"2013","journal-title":"Nature"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1038\/nature12606","article-title":"Autophagy Promotes Primary Ciliogenesis by Removing OFD1 from Centriolar Satellites","volume":"502","author":"Tang","year":"2013","journal-title":"Nature"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1080\/15548627.2015.1023983","article-title":"Reciprocal Regulation of Cilia and Autophagy via the MTOR and Proteasome Pathways","volume":"11","author":"Wang","year":"2015","journal-title":"Autophagy"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1038\/s41598-023-27766-2","article-title":"Mechanism of Cystogenesis by Cd79a-Driven, Conditional mTOR Activation in Developing Mouse Nephrons","volume":"13","author":"Matsuda","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_75","first-page":"158","article-title":"Autophagy Activators Suppress Cystogenesis in an Autosomal Dominant Polycystic Kidney Disease Model","volume":"26","author":"Zhu","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"F187","DOI":"10.1152\/ajprenal.00051.2019","article-title":"A Study of Sirolimus and mTOR Kinase Inhibitor in a Hypomorphic Pkd1 Mouse Model of Autosomal Dominant Polycystic Kidney Disease","volume":"317","author":"Holditch","year":"2019","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1111\/j.1440-1797.2012.01639.x","article-title":"Rapamycin-Mediated Suppression of Renal Cyst Expansion in Del34 Pkd1-\/- Mutant Mouse Embryos: An Investigation of the Feasibility of Renal Cyst Prevention in the Foetus","volume":"17","author":"Stayner","year":"2012","journal-title":"Nephrology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1111\/jcmm.13091","article-title":"Rapamycin Treatment Dose-Dependently Improves the Cystic Kidney in a New ADPKD Mouse Model via the mTORC1 and Cell-Cycle-Associated CDK1\/Cyclin Axis","volume":"21","author":"Li","year":"2017","journal-title":"J. Cell. Mol. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1146\/annurev-physiol-021119-034658","article-title":"Autophagy in Kidney Disease","volume":"82","author":"Choi","year":"2020","journal-title":"Annu. Rev. Physiol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s10157-016-1289-1","article-title":"Double Inhibition of cAMP and mTOR Signalling May Potentiate the Reduction of Cell Growth in ADPKD Cells","volume":"21","author":"Bonon","year":"2017","journal-title":"Clin. Exp. Nephrol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Tanaka, Y., Watari, M., Saito, T., Morishita, Y., and Ishibashi, K. (2016). Enhanced Autophagy in Polycystic Kidneys of AQP11 Null Mice. Int. J. Mol. Sci., 17.","DOI":"10.20944\/preprints201611.0066.v2"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Lee, E.J., Ko, J.Y., Oh, S., Jun, J., Mun, H., Lim, C.J., Seo, S., Ko, H.W., Kim, H., and Oh, Y.K. (2020). Autophagy Induction Promotes Renal Cyst Growth in Polycystic Kidney Disease. EBioMedicine, 60.","DOI":"10.1016\/j.ebiom.2020.102986"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Wang, S., and Dong, Z. (2020). Is Autophagy the Culprit of Cystogenesis in Polycystic Kidney Disease?. EBioMedicine, 61.","DOI":"10.1016\/j.ebiom.2020.103043"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s11655-018-2847-z","article-title":"Triptolide, A Potential Autophagy Modulator","volume":"25","author":"Wei","year":"2019","journal-title":"Chin. J. Integr. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"3157","DOI":"10.1002\/jcp.29227","article-title":"Modulatory Effects of Statins on the Autophagy: A Therapeutic Perspective","volume":"235","author":"Ashrafizadeh","year":"2020","journal-title":"J. Cell. Physiol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.bbamcr.2010.09.016","article-title":"Involvement of Caspase-9 in Autophagy-Mediated Cell Survival Pathway","volume":"1813","author":"Jeong","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1007\/s11033-018-4222-8","article-title":"Cyclin-Dependent Kinase Inhibitors, Roscovitine and Purvalanol, Induce Apoptosis and Autophagy Related to Unfolded Protein Response in HeLa Cervical Cancer Cells","volume":"45","author":"Sarikaya","year":"2018","journal-title":"Mol. Biol. Rep."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.bcp.2014.01.038","article-title":"Steviol Retards Renal Cyst Growth through Reduction of CFTR Expression and Inhibition of Epithelial Cell Proliferation in a Mouse Model of Polycystic Kidney Disease","volume":"88","author":"Yuajit","year":"2014","journal-title":"Biochem. Pharmacol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"4404","DOI":"10.1038\/s41467-021-24601-y","article-title":"TGF\u03b2 Promotes Fibrosis by MYST1-Dependent Epigenetic Regulation of Autophagy","volume":"12","author":"Zehender","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e1696","DOI":"10.1038\/cddis.2015.36","article-title":"Autophagy Is a Regulator of TGF-\u03921-Induced Fibrogenesis in Primary Human Atrial Myofibroblasts","volume":"6","author":"Ghavami","year":"2015","journal-title":"Cell Death Dis."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s42649-019-0012-6","article-title":"The Autophagy Research in Electron Microscopy","volume":"49","author":"Jung","year":"2019","journal-title":"Appl. Microsc."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1091\/mbc.e03-09-0704","article-title":"In Vivo Analysis of Autophagy in Response to Nutrient Starvation Using Transgenic Mice Expressing a Fluorescent Autophagosome Marker","volume":"15","author":"Mizushima","year":"2004","journal-title":"Mol. Biol. Cell."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1172\/JCI73937","article-title":"Pharmacologic Agents Targeting Autophagy","volume":"125","author":"Xia","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1056\/NEJMoa1003491","article-title":"Everolimus in Patients with Autosomal Dominant Polycystic Kidney Disease","volume":"363","author":"Walz","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1159\/000354398","article-title":"Long-Term Treatment with Mammalian Target of Rapamycin Inhibitor Does Not Benefit Patients with Autosomal Dominant Polycystic Kidney Disease: A Meta-Analysis","volume":"124","author":"Xue","year":"2013","journal-title":"Nephron. Clin. Pract."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.2165\/00002018-200629120-00006","article-title":"Sirolimus-Associated Proteinuria and Renal Dysfunction","volume":"29","author":"Rangan","year":"2006","journal-title":"Drug Saf."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1093\/ndt\/gfs453","article-title":"Sirolimus Reduces Vasculopathy but Exacerbates Proteinuria in Association with Inhibition of VEGF and VEGFR in a Rat Kidney Model of Chronic Allograft Dysfunction","volume":"28","author":"Ko","year":"2013","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1097\/TP.0b013e3182696a13","article-title":"Impact of Tacrolimus-Sirolimus Maintenance Immunosuppression on Proteinuria and Kidney Function in Pancreas Transplant Alone Recipients","volume":"94","author":"Kandula","year":"2012","journal-title":"Transplantation"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Krishnan, S., Shrestha, Y., Jayatunga, D.P.W., Rea, S., Martins, R., and Bharadwaj, P. (2020). Activate or Inhibit? Implications of Autophagy Modulation as a Therapeutic Strategy for Alzheimer\u2019s Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186739"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"5993","DOI":"10.2147\/IJGM.S305491","article-title":"Retarding Progression of Chronic Kidney Disease in Autosomal Dominant Polycystic Kidney Disease with Metformin and Other Therapies: An Update of New Insights","volume":"14","author":"Carullo","year":"2021","journal-title":"Int. J. Gen. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1042\/BST20200757","article-title":"The Cellular Pathways and Potential Therapeutics of Polycystic Kidney Disease","volume":"49","author":"Richards","year":"2021","journal-title":"Biochem. Soc. Trans."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"F27","DOI":"10.1152\/ajprenal.00298.2021","article-title":"Metformin Improves Relevant Disease Parameters in an Autosomal Dominant Polycystic Kidney Disease Mouse Model","volume":"322","author":"Li","year":"2022","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.cmet.2020.04.015","article-title":"Metformin Enhances Autophagy and Normalizes Mitochondrial Function to Alleviate Aging-Associated Inflammation","volume":"32","author":"Bharath","year":"2020","journal-title":"Cell Metab."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.kint.2021.06.013","article-title":"Primary Results of the Randomized Trial of Metformin Administration in Polycystic Kidney Disease (TAME PKD)","volume":"100","author":"Perrone","year":"2021","journal-title":"Kidney Int."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"507","DOI":"10.2215\/CJN.11260821","article-title":"Effects of Hydrochlorothiazide and Metformin on Aquaresis and Nephroprotection by a Vasopressin V2 Receptor Antagonist in ADPKD: A Randomized Crossover Trial","volume":"17","author":"Kramers","year":"2022","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_106","first-page":"325","article-title":"Vitamin D, Vitamin D Receptor, and Macroautophagy in Inflammation and Infection","volume":"11","author":"Wu","year":"2011","journal-title":"Discov. Med."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Bhutia, S.K. (2022). Vitamin D in Autophagy Signaling for Health and Diseases: Insights on Potential Mechanisms and Future Perspectives. J. Nutr. Biochem., 99.","DOI":"10.1016\/j.jnutbio.2021.108841"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"112","DOI":"10.3389\/fmed.2019.00112","article-title":"Association of Vitamin D Levels With Kidney Volume in Autosomal Dominant Polycystic Kidney Disease (ADPKD)","volume":"6","author":"Vendramini","year":"2019","journal-title":"Front. Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"2458","DOI":"10.1681\/ASN.2018060590","article-title":"A Practical Guide for Treatment of Rapidly Progressive ADPKD with Tolvaptan","volume":"29","author":"Chebib","year":"2018","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1111\/bph.14558","article-title":"The Combination of Metformin and 2-Deoxyglucose Significantly Inhibits Cyst Formation in Miniature Pigs with Polycystic Kidney Disease","volume":"176","author":"Lian","year":"2019","journal-title":"Br. J. Pharmacol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/19\/14666\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:00:19Z","timestamp":1760130019000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/19\/14666"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,28]]},"references-count":110,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["ijms241914666"],"URL":"https:\/\/doi.org\/10.3390\/ijms241914666","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,28]]}}}