{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T05:40:49Z","timestamp":1793943649494,"version":"4.8.0"},"reference-count":43,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T00:00:00Z","timestamp":1680739200000},"content-version":"vor","delay-in-days":370,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007957","name":"Chongqing Municipal Education Commission","doi-asserted-by":"publisher","award":["KJZD-K202000401"],"award-info":[{"award-number":["KJZD-K202000401"]}],"id":[{"id":"10.13039\/501100007957","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01DK078897"],"award-info":[{"award-number":["1R01DK078897"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01DK088541"],"award-info":[{"award-number":["1R01DK088541"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["81800731"],"award-info":[{"award-number":["81800731"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["82000810"],"award-info":[{"award-number":["82000810"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01-DK56492"],"award-info":[{"award-number":["P01-DK56492"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DK117913"],"award-info":[{"award-number":["R01 DK117913"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870567"],"award-info":[{"award-number":["81870567"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81970720"],"award-info":[{"award-number":["81970720"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy"],"published-print":{"date-parts":[[2022,4]]},"DOI":"10.1016\/j.ymthe.2021.10.013","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T23:58:16Z","timestamp":1634860696000},"page":"1741-1753","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":59,"title":["Kidney single-cell transcriptome profile reveals distinct response of proximal tubule cells to SGLT2i and ARB treatment in diabetic mice"],"prefix":"10.1016","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9168-1707","authenticated-orcid":false,"given":"Jinshan","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeguo","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shumin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8280-3813","authenticated-orcid":false,"given":"Jia","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niansong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinbo","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linqiang","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9756-1765","authenticated-orcid":false,"given":"Kyung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Cijiang","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qifu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ymthe.2021.10.013_bib1","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1001\/jama.2019.14745","article-title":"Chronic kidney disease diagnosis and management: a review","volume":"322","author":"Chen","year":"2019","journal-title":"JAMA"},{"key":"10.1016\/j.ymthe.2021.10.013_bib2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mcna.2012.10.001","article-title":"Epidemiology of diabetic kidney disease","volume":"97","author":"Reutens","year":"2013","journal-title":"Med. Clin. North Am."},{"key":"10.1016\/j.ymthe.2021.10.013_bib3","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1001\/jama.2013.284427","article-title":"2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8)","volume":"311","author":"James","year":"2014","journal-title":"JAMA"},{"key":"10.1016\/j.ymthe.2021.10.013_bib4","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1016\/S0140-6736(14)62459-4","article-title":"Comparative efficacy and safety of blood pressure-lowering agents in adults with diabetes and kidney disease: a network meta-analysis","volume":"385","author":"Palmer","year":"2015","journal-title":"The Lancet"},{"key":"10.1016\/j.ymthe.2021.10.013_bib5","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1056\/NEJMoa011303","article-title":"Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes","volume":"345","author":"Lewis","year":"2001","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.ymthe.2021.10.013_bib6","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1056\/NEJMoa1611925","article-title":"Canagliflozin and cardiovascular and renal events in type 2 diabetes","volume":"377","author":"Neal","year":"2017","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.ymthe.2021.10.013_bib7","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1056\/NEJMoa1515920","article-title":"Empagliflozin and progression of kidney disease in type 2 diabetes","volume":"375","author":"Wanner","year":"2016","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.ymthe.2021.10.013_bib8","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1056\/NEJMoa1812389","article-title":"Dapagliflozin and cardiovascular outcomes in type 2 diabetes","volume":"380","author":"Wiviott","year":"2019","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.ymthe.2021.10.013_bib9","doi-asserted-by":"crossref","first-page":"385","DOI":"10.7326\/M20-5938","article-title":"Diabetes management in chronic kidney disease: synopsis of the 2020 KDIGO clinical practice guideline","volume":"174","author":"Navaneethan","year":"2021","journal-title":"Ann. Intern. Med."},{"key":"10.1016\/j.ymthe.2021.10.013_bib10","doi-asserted-by":"crossref","first-page":"248","DOI":"10.2337\/dbi18-0007","article-title":"Sodium-glucose cotransporter 2 inhibition and diabetic kidney disease","volume":"68","author":"Alicic","year":"2019","journal-title":"Diabetes"},{"key":"10.1016\/j.ymthe.2021.10.013_bib11","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.kint.2017.12.027","article-title":"Renoprotective effects of sodium-glucose cotransporter-2 inhibitors","volume":"94","author":"Heerspink","year":"2018","journal-title":"Kidney Int."},{"key":"10.1016\/j.ymthe.2021.10.013_bib12","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.1681\/ASN.2019080770","article-title":"Single-cell RNA sequencing reveals mRNA splice isoform switching during kidney development","volume":"31","author":"Wineberg","year":"2020","journal-title":"J.\u00a0Am. Soc. Nephrol."},{"key":"10.1016\/j.ymthe.2021.10.013_bib13","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1126\/science.aar2131","article-title":"Single-cell transcriptomics of the mouse kidney reveals potential cellular targets of kidney disease","volume":"360","author":"Park","year":"2018","journal-title":"Science (New York, N.Y.)"},{"key":"10.1016\/j.ymthe.2021.10.013_bib14","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.cmet.2020.11.011","article-title":"The nuclear receptor ESRRA protects from kidney disease by coupling metabolism and differentiation","volume":"33","author":"Dhillon","year":"2021","journal-title":"Cell Metab"},{"key":"10.1016\/j.ymthe.2021.10.013_bib15","doi-asserted-by":"crossref","first-page":"2793","DOI":"10.1681\/ASN.2020010052","article-title":"Single-cell profiling of AKI in a murine model reveals novel transcriptional signatures, profibrotic phenotype, and epithelial-to-stromal crosstalk","volume":"31","author":"Rudman-Melnick","year":"2020","journal-title":"J.\u00a0Am. Soc. Nephrol."},{"key":"10.1016\/j.ymthe.2021.10.013_bib16","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1681\/ASN.2018090896","article-title":"Single-cell RNA profiling of glomerular cells shows dynamic changes in experimental diabetic kidney disease","volume":"30","author":"Fu","year":"2019","journal-title":"J.\u00a0Am. Soc. Nephrol."},{"key":"10.1016\/j.ymthe.2021.10.013_bib17","doi-asserted-by":"crossref","first-page":"19619","DOI":"10.1073\/pnas.1908706116","article-title":"The single-cell transcriptomic landscape of early human diabetic nephropathy","volume":"116","author":"Wilson","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"key":"10.1016\/j.ymthe.2021.10.013_bib18","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1038\/nm.3363","article-title":"Renal tubular Sirt1 attenuates diabetic albuminuria by epigenetically suppressing Claudin-1 overexpression in podocytes","volume":"19","author":"Hasegawa","year":"2013","journal-title":"Nat. Med."},{"key":"10.1016\/j.ymthe.2021.10.013_bib19","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.kint.2017.09.033","article-title":"Renal tubule injury: a driving force toward chronic kidney disease","volume":"93","author":"Liu","year":"2018","journal-title":"Kidney Int."},{"key":"10.1016\/j.ymthe.2021.10.013_bib20","doi-asserted-by":"crossref","first-page":"757","DOI":"10.2215\/CJN.04330418","article-title":"Clinical pharmacology of antihypertensive therapy for the treatment of hypertension in CKD","volume":"14","author":"Sinha","year":"2019","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"10.1016\/j.ymthe.2021.10.013_bib21","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1016\/j.kint.2016.06.032","article-title":"Loss of endogenous thymosin beta4 accelerates glomerular disease","volume":"90","author":"Vasilopoulou","year":"2016","journal-title":"Kidney Int."},{"key":"10.1016\/j.ymthe.2021.10.013_bib22","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1080\/03602530701468573","article-title":"Human cytochrome p450 family 4 enzymes: function, genetic variation and regulation","volume":"39","author":"Hsu","year":"2007","journal-title":"Drug Metab. Rev."},{"key":"10.1016\/j.ymthe.2021.10.013_bib23","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1097\/00008571-200207000-00004","article-title":"Genetic polymorphism of the human cytochrome P450 CYP4B1: evidence for a non-functional allelic variant","volume":"12","author":"Lo-Guidice","year":"2002","journal-title":"Pharmacogenetics"},{"key":"10.1016\/j.ymthe.2021.10.013_bib24","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.exphem.2007.11.003","article-title":"Reduction of AHSP synthesis in hemin-induced K562 cells and EPO-induced CD34(+) cells leads to alpha-globin precipitation, impairment of normal hemoglobin production, and increased cell death","volume":"36","author":"Pinho","year":"2008","journal-title":"Exp. Hematol."},{"key":"10.1016\/j.ymthe.2021.10.013_bib25","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1093\/cvr\/cvt207","article-title":"Cysteine-rich protein 2 alters p130Cas localization and inhibits vascular smooth muscle cell migration","volume":"100","author":"Chen","year":"2013","journal-title":"Cardiovasc. Res."},{"key":"10.1016\/j.ymthe.2021.10.013_bib26","doi-asserted-by":"crossref","first-page":"15003","DOI":"10.1074\/jbc.M801621200","article-title":"Transforming growth factor beta up-regulates cysteine-rich protein 2 in vascular smooth muscle cells via activating transcription factor 2","volume":"283","author":"Lin","year":"2008","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.ymthe.2021.10.013_bib27","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1056\/NEJMoa1811744","article-title":"Canagliflozin and renal outcomes in type 2 diabetes and nephropathy","volume":"380","author":"Perkovic","year":"2019","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.ymthe.2021.10.013_bib28","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1124\/jpet.120.000092","article-title":"Potent therapy and transcriptional profile of combined erythropoietin-derived peptide cyclic helix B surface peptide and caspase-3 siRNA against kidney ischemia\/reperfusion injury in mice","volume":"375","author":"Wu","year":"2020","journal-title":"J.\u00a0Pharmacol. Exp. Ther."},{"key":"10.1016\/j.ymthe.2021.10.013_bib29","doi-asserted-by":"crossref","DOI":"10.1186\/s41065-021-00176-y","article-title":"Bioinformatic analysis identifies potential biomarkers and therapeutic targets of septic-shock-associated acute kidney injury","volume":"158","author":"Tang","year":"2021","journal-title":"Hereditas"},{"key":"10.1016\/j.ymthe.2021.10.013_bib30","doi-asserted-by":"crossref","first-page":"11491","DOI":"10.18632\/aging.202841","article-title":"Comprehensive analysis of ferritin subunits expression and positive correlations with tumor-associated macrophages and T regulatory cells infiltration in most solid tumors","volume":"13","author":"Hu","year":"2021","journal-title":"Aging (Albany NY)"},{"key":"10.1016\/j.ymthe.2021.10.013_bib31","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/nrneph.2017.142","article-title":"Modelling diabetic nephropathy in mice","volume":"14","author":"Azushima","year":"2018","journal-title":"Nat. Rev. Nephrol."},{"key":"10.1016\/j.ymthe.2021.10.013_bib32","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1007\/s11886-019-1165-1","article-title":"Effect of SGLT2 inhibitors on the sympathetic nervous system and blood pressure","volume":"21","author":"Scheen","year":"2019","journal-title":"Curr. Cardiol. Rep."},{"key":"10.1016\/j.ymthe.2021.10.013_bib33","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s11906-019-0920-4","article-title":"Blood pressure lowering and sodium-glucose co-transporter 2 inhibitors (SGLT2is): more than osmotic diuresis","volume":"21","author":"Sternlicht","year":"2019","journal-title":"Curr. Hypertens. Rep."},{"key":"10.1016\/j.ymthe.2021.10.013_bib34","doi-asserted-by":"crossref","first-page":"791","DOI":"10.2337\/db16-0796","article-title":"Proximal tubulopathy: prime mover and key therapeutic target in diabetic kidney disease","volume":"66","author":"Gilbert","year":"2017","journal-title":"Diabetes"},{"key":"10.1016\/j.ymthe.2021.10.013_bib35","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1007\/s40620-017-0423-9","article-title":"A more tubulocentric view of diabetic kidney disease","volume":"30","author":"Zeni","year":"2017","journal-title":"J.\u00a0Nephrol."},{"key":"10.1016\/j.ymthe.2021.10.013_bib36","doi-asserted-by":"crossref","first-page":"900","DOI":"10.5301\/jn.5000134","article-title":"Renin-angiotensin-aldosterone system blockade for nephroprotection: current evidence and future directions","volume":"25","author":"Tylicki","year":"2012","journal-title":"J.\u00a0Nephrol."},{"key":"10.1016\/j.ymthe.2021.10.013_bib37","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1007\/s00467-011-2002-y","article-title":"The renin-angiotensin-aldosterone system in 2011: role in hypertension and chronic kidney disease","volume":"27","author":"Simoes","year":"2012","journal-title":"Pediatr. Nephrol."},{"key":"10.1016\/j.ymthe.2021.10.013_bib38","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.2353\/ajpath.2009.090698","article-title":"Endothelial-mesenchymal transition as a novel mechanism for generating myofibroblasts during diabetic nephropathy","volume":"175","author":"Kizu","year":"2009","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.ymthe.2021.10.013_bib39","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1111\/j.1440-1797.2010.01319.x","article-title":"Review: endothelial-myofibroblast transition, a new player in diabetic renal fibrosis","volume":"15","author":"Li","year":"2010","journal-title":"Nephrology (Carlton)"},{"key":"10.1016\/j.ymthe.2021.10.013_bib40","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1038\/s41581-019-0110-2","article-title":"Macrophages: versatile players in renal inflammation and fibrosis","volume":"15","author":"Tang","year":"2019","journal-title":"Nat. Rev. Nephrol."},{"key":"10.1016\/j.ymthe.2021.10.013_bib41","doi-asserted-by":"crossref","first-page":"2832","DOI":"10.1038\/s41467-019-10861-2","article-title":"A single-nucleus RNA-sequencing pipeline to decipher the molecular anatomy and pathophysiology of human kidneys","volume":"10","author":"Lake","year":"2019","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ymthe.2021.10.013_bib42","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s13238-020-00816-5","article-title":"Single-cell RNA-seq analysis identified kidney progenitor cells from human urine","volume":"12","author":"Wang","year":"2021","journal-title":"Protein Cell"},{"key":"10.1016\/j.ymthe.2021.10.013_bib43","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1681\/ASN.2018090912","article-title":"Advantages of single-nucleus over single-cell RNA sequencing of adult kidney: rare cell types and novel cell states revealed in fibrosis","volume":"30","author":"Wu","year":"2019","journal-title":"J.\u00a0Am. Soc. Nephrol."}],"container-title":["Molecular Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001621005207?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001621005207?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T18:01:56Z","timestamp":1761501716000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1525001621005207"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4]]},"references-count":43,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,4]]}},"alternative-id":["S1525001621005207"],"URL":"https:\/\/doi.org\/10.1016\/j.ymthe.2021.10.013","relation":{},"ISSN":["1525-0016"],"issn-type":[{"value":"1525-0016","type":"print"}],"subject":[],"published":{"date-parts":[[2022,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Kidney single-cell transcriptome profile reveals distinct response of proximal tubule cells to SGLT2i and ARB treatment in diabetic mice","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ymthe.2021.10.013","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 The American Society of Gene and Cell Therapy.","name":"copyright","label":"Copyright"}]}}