{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:10:27Z","timestamp":1760058627476,"version":"build-2065373602"},"reference-count":36,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T00:00:00Z","timestamp":1745193600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scientific Research (C) from the Ministry of Education, Science, Sports, and Culture in Japan","award":["17K09741","24590336","21590295","15590240","13670102","20K08601"],"award-info":[{"award-number":["17K09741","24590336","21590295","15590240","13670102","20K08601"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Although various factors contribute to the transition from acute kidney injury (AKI) to chronic kidney disease (CKD), no clinically effective pharmacological treatment has been established. We investigated whether chymase inhibition is effective in preventing renal fibrosis, a key process in the transition from AKI to CKD. Male BALB\/c mice were subjected to unilateral ischemia-reperfusion (I\/R) injury, and TY-51469, a chymase-specific inhibitor, was administered intraperitoneally at a dose of 10 mg\/kg\/day for 6 weeks. The 45 min ischemic period followed by 6 weeks of reperfusion resulted in severe renal atrophy. Renal fibrosis was particularly pronounced in the transition region between the cortex and medulla in placebo-treated mice. The expression of mouse mast cell protease 4 (MMCP-4, a mouse chymase) mRNA, the number of chymase-positive mast cells, and fibrosis-related factors, such as transforming growth factor (TGF)-\u03b21 and collagen I, were all significantly increased in I\/R-injured kidneys. However, treatment with TY-51469 significantly suppressed fibrosis formation, along with the inhibition of renal chymase and TGF-\u03b21 expression. These findings suggest that chymase inhibition may be a potential therapeutic strategy for preventing the transition from AKI to CKD by reducing fibrosis.<\/jats:p>","DOI":"10.3390\/ijms26083913","type":"journal-article","created":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T20:42:00Z","timestamp":1745268120000},"page":"3913","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chymase Inhibition Attenuates Kidney Fibrosis in a Chronic Mouse Model of Renal Ischemia\u2013Reperfusion Injury"],"prefix":"10.3390","volume":"26","author":[{"given":"Sakura","family":"Kure","sequence":"first","affiliation":[{"name":"Department of Innovative Medicine, Graduate School of Medicine, Osaka Medical and Pharmaceutical University, Takatsuki-City 569-8686, Osaka, Japan"},{"name":"Department of Nephrology, Osaka Medical and Pharmaceutical University, Takatsuki-City 569-8686, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3860-805X","authenticated-orcid":false,"given":"Hiroe","family":"Toba","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, 1 Misasagi Shichono-cho, Yamashina-ku 607-8412, Kyoto, Japan"},{"name":"Department of Pharmacology, Osaka Medical and Pharmaceutical University, Takatsuki-City 569-8686, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5820-8168","authenticated-orcid":false,"given":"Denan","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Innovative Medicine, Graduate School of Medicine, Osaka Medical and Pharmaceutical University, Takatsuki-City 569-8686, Osaka, Japan"},{"name":"Department of Pharmacology, Osaka Medical and Pharmaceutical University, Takatsuki-City 569-8686, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akira","family":"Mima","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Osaka Medical and Pharmaceutical University, Takatsuki-City 569-8686, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6196-4477","authenticated-orcid":false,"given":"Shinji","family":"Takai","sequence":"additional","affiliation":[{"name":"Department of Innovative Medicine, Graduate School of Medicine, Osaka Medical and Pharmaceutical University, Takatsuki-City 569-8686, Osaka, Japan"},{"name":"Department of Pharmacology, Osaka Medical and Pharmaceutical University, Takatsuki-City 569-8686, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.1097\/01.ASN.0000079785.13922.F6","article-title":"Recent advances in the pathophysiology of ischemic acute renal failure","volume":"14","author":"Bonventre","year":"2003","journal-title":"J. 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