{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T21:14:06Z","timestamp":1779138846929,"version":"3.51.4"},"reference-count":83,"publisher":"American Society for Clinical Investigation","issue":"1","license":[{"start":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T00:00:00Z","timestamp":1736380800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Veterans Affairs Biomedical Laboratory Research and Development Service Merit Review Award","award":["I01 BX001340,5I01 BX000926,1I01BX003234"],"award-info":[{"award-number":["I01 BX001340,5I01 BX000926,1I01BX003234"]}]},{"name":"Research Career Scientist Award","award":["IK6BX005795"],"award-info":[{"award-number":["IK6BX005795"]}]},{"name":"NIH","award":["R01DE017102,R01DE022765"],"award-info":[{"award-number":["R01DE017102,R01DE022765"]}]},{"name":"Institutional Development Award (IDeA) from NIGMS under","award":["P20GM121307"],"award-info":[{"award-number":["P20GM121307"]}]},{"name":"George O\u2019Brien Michigan Kidney Translational Core Center at University of Michigan, funded by NIH\/NIDDK","award":["2P30-DK-081943"],"award-info":[{"award-number":["2P30-DK-081943"]}]},{"name":"NIH","award":["UH3DK114920,UO1DK114920,"],"award-info":[{"award-number":["UH3DK114920,UO1DK114920,"]}]},{"name":"NIH","award":["U54DK137314-02"],"award-info":[{"award-number":["U54DK137314-02"]}]},{"name":"DOD","award":["HT94252410202"],"award-info":[{"award-number":["HT94252410202"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,9]]},"abstract":"<jats:p>\n                    The role played by anionic channels in diabetic kidney disease (DKD) is not known. Chloride channel accessory 1 (CLCA1) facilitates the activity of TMEM16A (Anoctamin-1), a Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -dependent Cl\n                    <jats:sup>\u2013<\/jats:sup>\n                    channel. We examined if CLCA1\/TMEM16A had a role in DKD. In mice with type 2 diabetes, renal cortical CLCA1 and TMEM16A content was increased. CLCA1 and TMEM16A content was associated with hydrogen sulfide (H\n                    <jats:sub>2<\/jats:sub>\n                    S) deficiency, mTOR complex 1 (mTORC1) activation, albuminuria, and matrix increase. Administering sodium hydrosulfide (NaHS), a source of H\n                    <jats:sub>2<\/jats:sub>\n                    S, mitigated these changes. In proximal tubular epithelial (MCT) cells, high glucose rapidly increased CLCA1 by recruiting the IL-6\/STAT3 axis and augmented TMEM16A expression by stimulating its mRNA translation; these changes were abolished by NaHS. Patch clamp experiments showed that high glucose increased Cl\n                    <jats:sup>\u2013<\/jats:sup>\n                    current in MCT cells that was ameliorated by NaHS and a TMEM16A chemical inhibitor. siRNA against CLCA1 or TMEM16A and TMEM16A inhibitor abolished high glucose\u2013induced mTORC1 activation and matrix protein increase. Tubular expression of\n                    <jats:italic>TMEM16A<\/jats:italic>\n                    correlated with albuminuria in kidney biopsies from people with type 2 diabetes. We report a pathway for DKD in which H\n                    <jats:sub>2<\/jats:sub>\n                    S deficiency results in kidney injury by the recruitment of the CLCA1\/TMEM16A\/Cl\n                    <jats:sup>\u2013<\/jats:sup>\n                    current system.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.174848","type":"journal-article","created":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T14:00:42Z","timestamp":1736344842000},"source":"Crossref","is-referenced-by-count":2,"title":["The CLCA1\/TMEM16A\/Cl\u2013 current axis associates with H2S deficiency in diabetic kidney injury"],"prefix":"10.1172","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3954-3216","authenticated-orcid":true,"given":"Hak Joo","family":"Lee","sequence":"first","affiliation":[{"name":"Center for Precision Medicine, Department of Medicine, 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G.","family":"Kevil","sequence":"additional","affiliation":[{"name":"Department of Pathology, Louisiana State University Health Science Center, Shreveport, Louisiana, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shankara","family":"Varadarajan","sequence":"additional","affiliation":[{"name":"Department of Periodontics, University of Texas Health, San Antonio, San Antonio, Texas, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6557-4521","authenticated-orcid":true,"given":"Guanshi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Precision Medicine, Department of Medicine, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Goutam","family":"Ghosh Choudhury","sequence":"additional","affiliation":[{"name":"Center for Precision Medicine, Department of Medicine, and"},{"name":"Research service and"},{"name":"Geriatric Research Education and Clinical Center, South Texas 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