{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:17:28Z","timestamp":1791407848934,"version":"4.3.3"},"reference-count":46,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,29]],"date-time":"2020-12-29T00:00:00Z","timestamp":1609200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1058175"],"award-info":[{"award-number":["1058175"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Australian Postgraduate Award","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cyclophilins have important homeostatic roles, but following tissue injury, cyclophilin A (CypA) can promote leukocyte recruitment and inflammation, while CypD can facilitate mitochondrial-dependent cell death. This study investigated the therapeutic potential of a selective cyclophilin inhibitor (GS-642362), which does not block calcineurin function, in mouse models of tubular cell necrosis and renal fibrosis. Mice underwent bilateral renal ischemia\/reperfusion injury (IRI) and were killed 24 h later: treatment with 10 or 30 mg\/kg\/BID GS-642362 (or vehicle) began 1 h before surgery. In the second model, mice underwent unilateral ureteric obstruction (UUO) surgery and were killed 7 days later; treatment with 10 or 30 mg\/kg\/BID GS-642362 (or vehicle) began 1 h before surgery. GS-642362 treatment gave a profound and dose-dependent protection from acute renal failure in the IRI model. This protection was associated with reduced tubular cell death, including a dramatic reduction in neutrophil infiltration. In the UUO model, GS-642362 treatment significantly reduced tubular cell death, macrophage infiltration, and renal fibrosis. This protective effect was independent of the upregulation of IL-2 and activation of the stress-activated protein kinases (p38 and JNK). In conclusion, GS-642362 was effective in suppressing both acute kidney injury and renal fibrosis. These findings support further investigation of cyclophilin blockade in other types of acute and chronic kidney disease.<\/jats:p>","DOI":"10.3390\/ijms22010271","type":"journal-article","created":{"date-parts":[[2020,12,29]],"date-time":"2020-12-29T19:55:25Z","timestamp":1609271725000},"page":"271","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Cyclophilin Inhibition Protects Against Experimental Acute Kidney Injury and Renal Interstitial Fibrosis"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1944-9663","authenticated-orcid":false,"given":"Khai Gene","family":"Leong","sequence":"first","affiliation":[{"name":"Monash Medical Centre, Department of Nephrology, Clayton, VIC 3168, Australia"},{"name":"Centre for Inflammatory Diseases, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elyce","family":"Ozols","sequence":"additional","affiliation":[{"name":"Monash Medical Centre, Department of Nephrology, Clayton, VIC 3168, Australia"},{"name":"Centre for Inflammatory Diseases, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Kanellis","sequence":"additional","affiliation":[{"name":"Monash Medical Centre, Department of Nephrology, Clayton, VIC 3168, Australia"},{"name":"Centre for Inflammatory Diseases, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn S.","family":"Badal","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Foster City, CA 94404, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John T.","family":"Liles","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Foster City, CA 94404, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5734-2931","authenticated-orcid":false,"given":"David J.","family":"Nikolic-Paterson","sequence":"additional","affiliation":[{"name":"Monash Medical Centre, Department of Nephrology, Clayton, VIC 3168, Australia"},{"name":"Centre for Inflammatory Diseases, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank Y.","family":"Ma","sequence":"additional","affiliation":[{"name":"Monash Medical Centre, Department of Nephrology, Clayton, VIC 3168, Australia"},{"name":"Centre for Inflammatory Diseases, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/728673","article-title":"The Roles of CD147 and\/or Cyclophilin A in Kidney Diseases","volume":"2014","author":"Qu","year":"2014","journal-title":"Mediat. 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