{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T06:50:59Z","timestamp":1779346259840,"version":"3.51.4"},"reference-count":48,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2020,10,11]],"date-time":"2020-10-11T00:00:00Z","timestamp":1602374400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Voucher","award":["6baa4bd9cb53c4b8"],"award-info":[{"award-number":["6baa4bd9cb53c4b8"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chymase has several functions, such as angiotensin II formation, which can promote diabetic kidney disease (DKD). In this study, we evaluated the effect of the chymase inhibitor TY-51469 on DKD in diabetic db\/db mice. Diabetic mice were administered TY-51469 (10 mg\/kg\/day) or placebo for 4 weeks. No significant difference was observed in body weight and fasting blood glucose between TY-51469- and placebo-treated groups. However, a significant reduction in urinary albumin\/creatinine ratio was observed in the TY-51469-treated group compared with the placebo-treated group. In the renal extract, chymase activity was significantly higher in placebo-treated mice than in non-diabetic db\/m mice, but it was reduced by treatment with TY-51469. Both NADPH oxidase 4 expression and the oxidative stress marker malondialdehyde were significantly augmented in the placebo-treated group, but they were attenuated in the TY-51469-treated group. Significant increases of tumor necrosis factor-\u03b1 and transforming growth factor-\u03b2 mRNA levels in the placebo-treated group were significantly reduced by treatment with TY-51469. Furthermore, the expression of nephrin, which is a podocyte-specific protein, was significantly reduced in the placebo-treated group, but it was restored in the TY-51469-treated group. These findings demonstrated that chymase inhibition reduced albuminuria via attenuation of podocyte injury by oxidative stress.<\/jats:p>","DOI":"10.3390\/ijms21207495","type":"journal-article","created":{"date-parts":[[2020,10,13]],"date-time":"2020-10-13T21:48:38Z","timestamp":1602625718000},"page":"7495","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Mechanism of Albuminuria Reduction by Chymase Inhibition in Diabetic Mice"],"prefix":"10.3390","volume":"21","author":[{"given":"Kentaro","family":"Terai","sequence":"first","affiliation":[{"name":"Department of Innovative Medicine, Graduate School of Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan"},{"name":"Department of Internal Medicine (I), Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denan","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Innovative Medicine, Graduate School of Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Watase","sequence":"additional","affiliation":[{"name":"Department of Innovative Medicine, Graduate School of Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akihisa","family":"Imagawa","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (I), Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3963-3983","authenticated-orcid":false,"given":"Shinji","family":"Takai","sequence":"additional","affiliation":[{"name":"Department of Innovative Medicine, Graduate School of Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1159\/000489913","article-title":"Effects of Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on all-cause mortality and renal outcomes in patients with diabetes and albuminuria: A systematic review and meta-analysis","volume":"43","author":"Wang","year":"2018","journal-title":"Kidney Blood Press. 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