{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:00:26Z","timestamp":1791388826106,"version":"4.3.3"},"reference-count":60,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T00:00:00Z","timestamp":1623283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"KAKENHI, Grant-in-Aid for Challenging Exploratory Research","award":["20K21773"],"award-info":[{"award-number":["20K21773"]}]},{"name":"AstraZeneca K.K. and Ono Pharmaceutical Co. Ltd.","award":["NCR-17-12737"],"award-info":[{"award-number":["NCR-17-12737"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Sodium-glucose cotransporter2 (SGLT2) inhibitors have a reno-protective effect in diabetic kidney disease. However, the detailed mechanism remains unclear. In this study, human proximal tubular cells (HK-2) were cultured in 5 mM glucose and 25 mM mannitol (control), 30 mM glucose (high glucose: HG), or HG and SGLT2 inhibitor, dapagliflozin-containing medium for 48 h. The autophagic flux was decreased, accompanied by the increased phosphorylation of S6 kinase ribosomal protein (p-S6RP) and the reduced phosphorylation of AMP-activated kinase (p-AMPK) expression in a HG condition. Compared to those of the control, dapagliflozin and SGLT2 knockdown ameliorated the HG-induced alterations of p-S6RP, p-AMPK, and autophagic flux. In addition, HG increased the nuclear translocation of nuclear factor-\u03baB p65 (NF-\u03baB) p65 and the cytoplasmic nucleotide-binding oligomerization domain-like receptor 3 (NLRP3), mature interleukin-1\u03b2 (IL-1\u03b2), IL-6, and tumor necrosis factor\u03b1 (TNF\u03b1) expression. Dapagliflozin, SGLT2 knockdown, and NF-\u03baB p65 knockdown reduced the extent of these HG-induced inflammatory alterations. The inhibitory effect of dapagliflozin on the increase in the HG-induced nuclear translocation of NF-\u03baB p65 was abrogated by knocking down AMPK. These data indicated that in diabetic renal proximal tubular cells, dapagliflozin ameliorates: (1) HG-induced autophagic flux reduction, via increased AMPK activity and mTOR suppression; and (2) inflammatory alterations due to NF-\u03baB pathway suppression.<\/jats:p>","DOI":"10.3390\/cells10061457","type":"journal-article","created":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T13:31:39Z","timestamp":1623331899000},"page":"1457","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":118,"title":["Dapagliflozin Restores Impaired Autophagy and Suppresses Inflammation in High Glucose-Treated HK-2 Cells"],"prefix":"10.3390","volume":"10","author":[{"given":"Jing","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Diabetology and Endocrinology, Kanazawa Medical University, Uchinada, Kahoku 920-0293, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3854-1385","authenticated-orcid":false,"given":"Munehiro","family":"Kitada","sequence":"additional","affiliation":[{"name":"Department of Diabetology and Endocrinology, Kanazawa Medical University, Uchinada, Kahoku 920-0293, Ishikawa, Japan"},{"name":"Division of Anticipatory Molecular Food Science and Technology, Medical Research Institute, Kanazawa Medical University, Uchinada, Kahoku 920-0293, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Ogura","sequence":"additional","affiliation":[{"name":"Department of Diabetology and Endocrinology, Kanazawa Medical University, Uchinada, Kahoku 920-0293, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijie","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Diabetology and Endocrinology, Kanazawa Medical University, Uchinada, Kahoku 920-0293, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2711-1539","authenticated-orcid":false,"given":"Daisuke","family":"Koya","sequence":"additional","affiliation":[{"name":"Department of Diabetology and Endocrinology, Kanazawa Medical University, Uchinada, Kahoku 920-0293, Ishikawa, Japan"},{"name":"Division of Anticipatory Molecular Food Science and Technology, Medical Research Institute, Kanazawa Medical University, Uchinada, Kahoku 920-0293, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2864","DOI":"10.2337\/dc14-1296","article-title":"Diabetic kidney disease: A report from an ADA Consensus Conference","volume":"37","author":"Tuttle","year":"2014","journal-title":"Diabetes Care"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrneph.2016.170","article-title":"Renal, metabolic and cardiovascular considerations of SGLT2 inhibition","volume":"13","author":"DeFronzo","year":"2017","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"650","DOI":"10.2337\/dc08-1863","article-title":"Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes","volume":"32","author":"List","year":"2009","journal-title":"Diabetes Care"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S2213-8587(15)00417-9","article-title":"Blood pressure and glycaemic effects of dapagliflozin versus placebo in patients with type 2 diabetes on combination antihypertensive therapy: A randomised, double-blind, placebo-controlled, phase 3 study","volume":"4","author":"Weber","year":"2016","journal-title":"Lancet. Diabetes Endocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1016\/S2213-8587(19)30180-9","article-title":"Effects of dapagliflozin on development and progression of kidney disease in patients with type 2 diabetes: An analysis from the DECLARE-TIMI 58 randomised trial","volume":"7","author":"Mosenzon","year":"2019","journal-title":"Lancet. Diabetes Endocrinol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/j.cmet.2019.10.008","article-title":"The DAPA-HF Trial: A Momentous Victory in the War against Heart Failure","volume":"30","author":"Bhatt","year":"2019","journal-title":"Cell Metab"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1056\/NEJMoa1911303","article-title":"Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction","volume":"381","author":"McMurray","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1056\/NEJMoa2024816","article-title":"Dapagliflozin in Patients with Chronic Kidney Disease","volume":"383","author":"Heerspink","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1681\/ASN.2020010010","article-title":"Role of Impaired Nutrient and Oxygen Deprivation Signaling and Deficient Autophagic Flux in Diabetic CKD Development: Implications for Understanding the Effects of Sodium-Glucose Cotransporter 2-Inhibitors","volume":"31","author":"Packer","year":"2020","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1038\/s41581-019-0234-4","article-title":"Innate immunity in diabetic kidney disease","volume":"16","author":"Tang","year":"2020","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.molcel.2017.05.032","article-title":"AMPK: Mechanisms of Cellular Energy Sensing and Restoration of Metabolic Balance","volume":"66","author":"Garcia","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/j.cell.2011.10.026","article-title":"Autophagy: Renovation of cells and tissues","volume":"147","author":"Mizushima","year":"2011","journal-title":"Cell"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Packer, M. (2020). Interplay of AMPK\/SIRT1 Activation and Sodium Influx Inhibition Mediates the Renal Benefits of SGLT2 Inhibitors in Type 2 Diabetes: A Novel Conceptual Framework. Diabetes Obes. Metab.","DOI":"10.1111\/dom.13961"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2784","DOI":"10.2337\/db16-0058","article-title":"The Na+\/Glucose Cotransporter Inhibitor Canagliflozin Activates AMPK by Inhibiting Mitochondrial Function and Increasing Cellular AMP Levels","volume":"65","author":"Hawley","year":"2016","journal-title":"Diabetes"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"F767","DOI":"10.1152\/ajprenal.00565.2018","article-title":"Empagliflozin attenuates diabetic tubulopathy by improving mitochondrial fragmentation and autophagy","volume":"317","author":"Lee","year":"2019","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Jaikumkao, K., Promsan, S., Thongnak, L., Swe, M.T., Tapanya, M., Htun, K.T., Kothan, S., Intachai, N., and Lungkaphin, A. (2021). Dapagliflozin ameliorates pancreatic injury and activates kidney autophagy by modulating the AMPK\/mTOR signaling pathway in obese rats. J. Cell. Physiol.","DOI":"10.1002\/jcp.30316"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1172\/JCI25102","article-title":"Inflammation, stress, and diabetes","volume":"115","author":"Wellen","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Liu, T., Zhang, L., Joo, D., and Sun, S.C. (2017). NF-kappaB signaling in inflammation. Signal Transduct. Target., 2.","DOI":"10.1038\/sigtrans.2017.23"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/S1734-1140(09)70111-2","article-title":"Role of NF-kappa B in the pathogenesis of diabetes and its associated complications","volume":"61","author":"Patel","year":"2009","journal-title":"Pharmacol. Rep. PR"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Panchapakesan, U., Pegg, K., Gross, S., Komala, M.G., Mudaliar, H., Forbes, J., Pollock, C., and Mather, A. (2013). Effects of SGLT2 inhibition in human kidney proximal tubular cells--renoprotection in diabetic nephropathy?. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0054442"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1016\/j.febslet.2012.02.045","article-title":"TLR-induced NF-kappaB activation regulates NLRP3 expression in murine macrophages","volume":"586","author":"Qiao","year":"2012","journal-title":"Febs Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"618231","DOI":"10.3389\/fimmu.2020.618231","article-title":"Regulation of the NLRP3 Inflammasome by Post-Translational Modifications and Small Molecules","volume":"11","author":"Seok","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.phrs.2016.11.004","article-title":"Roles of the NLRP3 inflammasome in the pathogenesis of diabetic nephropathy","volume":"114","author":"Qiu","year":"2016","journal-title":"Pharmacol. Res."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Fang, L., Xie, D., Wu, X., Cao, H., Su, W., and Yang, J. (2013). Involvement of endoplasmic reticulum stress in albuminuria induced inflammasome activation in renal proximal tubular cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0072344"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/nature11862","article-title":"Metabolism of inflammation limited by AMPK and pseudo-starvation","volume":"493","author":"Hardie","year":"2013","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s10557-017-6725-2","article-title":"SGLT-2 Inhibition with Dapagliflozin Reduces the Activation of the Nlrp3\/ASC Inflammasome and Attenuates the Development of Diabetic Cardiomyopathy in Mice with Type 2 Diabetes. Further Augmentation of the Effects with Saxagliptin, a DPP4 Inhibitor","volume":"31","author":"Ye","year":"2017","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1038\/s41467-020-15983-6","article-title":"SGLT2 inhibition modulates NLRP3 inflammasome activity via ketones and insulin in diabetes with cardiovascular disease","volume":"11","author":"Kim","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"104870","DOI":"10.1016\/j.phrs.2020.104870","article-title":"Empagliflozin protects heart from inflammation and energy depletion via AMPK activation","volume":"158","author":"Koyani","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/ki.1994.6","article-title":"HK-2: An immortalized proximal tubule epithelial cell line from normal adult human kidney","volume":"45","author":"Ryan","year":"1994","journal-title":"Kidney Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s13659-018-0188-4","article-title":"A Fluorescent Glucose Transport Assay for Screening SGLT2 Inhibitors in Endogenous SGLT2-Expressing HK-2 Cells","volume":"9","author":"Lu","year":"2019","journal-title":"Nat. Prod. Bioprospect."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Zaibi, N., Li, P., and Xu, S.Z. (2021). Protective effects of dapagliflozin against oxidative stress-induced cell injury in human proximal tubular cells. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0247234"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"109506","DOI":"10.1016\/j.cellsig.2019.109506","article-title":"Empagliflozin reduces high glucose-induced oxidative stress and miR-21-dependent TRAF3IP2 induction and RECK suppression, and inhibits human renal proximal tubular epithelial cell migration and epithelial-to-mesenchymal transition","volume":"68","author":"Das","year":"2020","journal-title":"Cell. Signal."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Li, J., Liu, H., Takagi, S., Nitta, K., Kitada, M., Srivastava, S.P., Takagaki, Y., Kanasaki, K., and Koya, D. (2020). Renal protective effects of empagliflozin via inhibition of EMT and aberrant glycolysis in proximal tubules. JCI Insight, 5.","DOI":"10.1172\/jci.insight.129034"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"14754","DOI":"10.1038\/s41598-019-51343-1","article-title":"Hypoxia-inducible factor-1\u03b1 is the therapeutic target of the SGLT2 inhibitor for diabetic nephropathy","volume":"9","author":"Bessho","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/nature09932","article-title":"Structure of mammalian AMPK and its regulation by ADP","volume":"472","author":"Xiao","year":"2011","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1161\/CIRCULATIONAHA.119.045561","article-title":"Role of Deranged Energy Deprivation Signaling in the Pathogenesis of Cardiac and Renal Disease in States of Perceived Nutrient Overabundance","volume":"141","author":"Packer","year":"2020","journal-title":"Circulation"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"154334","DOI":"10.1016\/j.metabol.2020.154334","article-title":"Empagliflozin improves diabetic renal tubular injury by alleviating mitochondrial fission via AMPK\/SP1\/PGAM5 pathway","volume":"111","author":"Liu","year":"2020","journal-title":"Metab. Clin. Exp."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Lee, J.Y., Lee, M., Lee, J.Y., Bae, J., Shin, E., Lee, Y.H., Lee, B.W., Kang, E.S., and Cha, B.S. (2021). Ipragliflozin, an SGLT2 Inhibitor, Ameliorates High-Fat Diet-Induced Metabolic Changes by Upregulating Energy Expenditure through Activation of the AMPK\/SIRT1 Pathway. Diabetes Metab. J.","DOI":"10.4093\/dmj.2020.0187"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s11892-017-0879-y","article-title":"Regulating Autophagy as a Therapeutic Target for Diabetic Nephropathy","volume":"17","author":"Kitada","year":"2017","journal-title":"Curr. Diabetes Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2493","DOI":"10.1681\/ASN.2008111186","article-title":"The role of the mammalian target of rapamycin (mTOR) in renal disease","volume":"20","author":"Lieberthal","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.bbrc.2005.12.012","article-title":"Inhibition of mTOR signaling with rapamycin attenuates renal hypertrophy in the early diabetic mice","volume":"340","author":"Sakaguchi","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1007\/s00125-016-3925-4","article-title":"A very-low-protein diet ameliorates advanced diabetic nephropathy through autophagy induction by suppression of the mTORC1 pathway in Wistar fatty rats, an animal model of type 2 diabetes and obesity","volume":"59","author":"Kitada","year":"2016","journal-title":"Diabetologia"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s12986-018-0255-1","article-title":"A low-protein diet exerts a beneficial effect on diabetic status and prevents diabetic nephropathy in Wistar fatty rats, an animal model of type 2 diabetes and obesity","volume":"15","author":"Kitada","year":"2018","journal-title":"Nutr. Metab."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4489","DOI":"10.18632\/aging.102902","article-title":"Methionine abrogates the renoprotective effect of a low-protein diet against diabetic kidney disease in obese rats with type 2 diabetes","volume":"12","author":"Kitada","year":"2020","journal-title":"Aging"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1681\/ASN.2018100983","article-title":"Proximal Tubule Autophagy Differs in Type 1 and 2 Diabetes","volume":"30","author":"Sakai","year":"2019","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.bcp.2018.03.013","article-title":"Canagliflozin exerts anti-inflammatory effects by inhibiting intracellular glucose metabolism and promoting autophagy in immune cells","volume":"152","author":"Xu","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_47","first-page":"3049","article-title":"The pathogenic role of the renal proximal tubular cell in diabetic nephropathy","volume":"27","author":"Tang","year":"2012","journal-title":"Nephrol. Dial. Transplant. Off. Publ. Eur. Dial. Transpl. Assoc. Eur. Ren. Assoc."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Matoba, K., Takeda, Y., Nagai, Y., Kawanami, D., Utsunomiya, K., and Nishimura, R. (2019). Unraveling the Role of Inflammation in the Pathogenesis of Diabetic Kidney Disease. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20143393"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1159\/000493278","article-title":"Inflammation in Diabetic Kidney Disease","volume":"143","author":"Valdivielso","year":"2019","journal-title":"Nephron"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5335","DOI":"10.1074\/jbc.M117.779520","article-title":"SGLT2 Protein Expression Is Increased in Human Diabetic Nephropathy: Sglt2 protein inhibition decreases renal lipid accumulation, inflammation, and the development of nephropathy in diabetic mice","volume":"292","author":"Wang","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2617","DOI":"10.1111\/dom.13441","article-title":"Dapagliflozin, a sodium-glucose co-transporter-2 inhibitor, slows the progression of renal complications through the suppression of renal inflammation, endoplasmic reticulum stress and apoptosis in prediabetic rats","volume":"20","author":"Jaikumkao","year":"2018","journal-title":"Diabetes Obes. Metab."},{"key":"ref_52","first-page":"3625","article-title":"Renoprotection of dapagliflozin in human renal proximal tubular cells via the inhibition of the high mobility group box 1-receptor for advanced glycation end products-nuclear factor-\u03baB signaling pathway","volume":"18","author":"Yao","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1111\/nep.12785","article-title":"The NLRP3 inflammasome in kidney disease and autoimmunity","volume":"21","author":"Hutton","year":"2016","journal-title":"Nephrol. (CarltonVic.)"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"429","DOI":"10.21037\/atm.2019.09.03","article-title":"The SGLT2 inhibitor dapagliflozin attenuates the activity of ROS-NLRP3 inflammasome axis in steatohepatitis with diabetes mellitus","volume":"7","author":"Leng","year":"2019","journal-title":"Ann. Transl. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"6305735","DOI":"10.1155\/2016\/6305735","article-title":"The SGLT-2 Inhibitor Dapagliflozin Has a Therapeutic Effect on Atherosclerosis in Diabetic ApoE(-\/-) Mice","volume":"2016","author":"Leng","year":"2016","journal-title":"Mediat. Inflamm."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"109825","DOI":"10.1016\/j.cellsig.2020.109825","article-title":"The SGLT2 inhibitor Empagliflozin attenuates interleukin-17A-induced human aortic smooth muscle cell proliferation and migration by targeting TRAF3IP2\/ROS\/NLRP3\/Caspase-1-dependent IL-1\u03b2 and IL-18 secretion","volume":"77","author":"Sukhanov","year":"2021","journal-title":"Cell. Signal."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.tem.2017.10.009","article-title":"AMP-Activated Protein Kinase Regulation of the NLRP3 Inflammasome during Aging","volume":"29","author":"Cordero","year":"2018","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"173449","DOI":"10.1016\/j.ejphar.2020.173449","article-title":"Geniposide alleviates diabetic nephropathy of mice through AMPK\/SIRT1\/NF-\u03baB pathway","volume":"886","author":"Li","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.bbrc.2012.09.042","article-title":"SIRT1 inactivation induces inflammation through the dysregulation of autophagy in human THP-1 cells","volume":"427","author":"Kitada","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"172797","DOI":"10.1016\/j.ejphar.2019.172797","article-title":"Salidroside ameliorates endothelial inflammation and oxidative stress by regulating the AMPK\/NF-\u03baB\/NLRP3 signaling pathway in AGEs-induced HUVECs","volume":"867","author":"Hu","year":"2020","journal-title":"Eur. J. Pharmacol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/6\/1457\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:12:58Z","timestamp":1760163178000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/6\/1457"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,10]]},"references-count":60,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["cells10061457"],"URL":"https:\/\/doi.org\/10.3390\/cells10061457","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,10]]}}}