{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T10:15:11Z","timestamp":1792059311600,"version":"4.4.0"},"reference-count":15,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,8,30]],"date-time":"2020-08-30T00:00:00Z","timestamp":1598745600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873617"],"award-info":[{"award-number":["81873617"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:p>Chronic kidney disease (CKD) is a worldwide public health problem that is caused by repeated injuries to the glomerulus or renal tubules. Renal fibrosis commonly accompanies CKD, and it is histologically characterized by excessive deposition of extracellular matrix proteins, such as fibronectin and collagen I, in interstitial areas. Indirect <jats:italic>in\u00a0vivo<\/jats:italic> experimental data suggest that renal asymmetric dimethylarginine (ADMA) exerts antifibrotic activity in CKD. In this study, we aimed to demonstrate that renal ADMA has a direct effect on fibrosis <jats:italic>in\u00a0vivo<\/jats:italic>. Normal saline, ADMA, nonsense control siRNA, Ddah1 siRNA or Ddah2 siRNA was administered into the kidney through the left ureter in a mouse model of unilateral ureteral obstruction (UUO). UUO kidneys were harvested at day 1 or 7. Western blotting was performed to assess the expression of ADMA, DDAH1 and DDAH2 and the expression of fibrotic markers, such as fibronectin, collagen I, \u03b1\u2010smooth muscle actin, phosphorylation of Smad3 and connective tissue growth factor. Masson\u2019s trichrome staining was used to further evaluate renal fibrosis. We observed that intrarenal administration of ADMA increased the renal accumulation of ADMA and attenuated renal fibrosis at days 1 and 7. Knockdown of <jats:italic>Ddah1<\/jats:italic> or <jats:italic>Ddah2<\/jats:italic> increased the amount of ADMA in UUO kidneys and inhibited the expression of fibrotic proteins at days 1 and 7, which was further confirmed by Masson\u2019s staining. Thus, our <jats:italic>in\u00a0vivo<\/jats:italic> data suggest that renal ADMA exerts direct antifibrotic effects in a mouse model of UUO.<\/jats:p>","DOI":"10.1002\/2211-5463.12949","type":"journal-article","created":{"date-parts":[[2020,8,15]],"date-time":"2020-08-15T04:51:16Z","timestamp":1597467076000},"page":"2003-2009","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Renal asymmetric dimethylarginine inhibits fibrosis"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8095-8766","authenticated-orcid":false,"given":"Ming","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Nephrology TCM Institute of Kidney Disease of Shanghai University of Traditional Chinese Medicine Key Laboratory of Liver and Kidney Diseases Ministry of Education Shanghai Key Laboratory of Traditional Chinese Clinical Medicine Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0951-8271","authenticated-orcid":false,"given":"Meijie","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Nephrology TCM Institute of Kidney Disease of Shanghai University of Traditional Chinese Medicine Key Laboratory of Liver and Kidney Diseases Ministry of Education Shanghai Key Laboratory of Traditional Chinese Clinical Medicine Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine China"},{"name":"Department of Nephrology The First Hospital of Hebei Medical University Shijiazhuang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanzhe","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nephrology TCM Institute of Kidney Disease of Shanghai University of Traditional Chinese Medicine Key Laboratory of Liver and Kidney Diseases Ministry of Education Shanghai Key Laboratory of Traditional Chinese Clinical Medicine Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine China"},{"name":"College of Integrated Traditional Chinese and Western Medicine Hebei University of Chinese Medicine Shijiazhuang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Tan","sequence":"additional","affiliation":[{"name":"Clinical Pharmacokinetic Laboratory Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Nephrology TCM Institute of Kidney Disease of Shanghai University of Traditional Chinese Medicine Key Laboratory of Liver and Kidney Diseases Ministry of Education Shanghai Key Laboratory of Traditional Chinese Clinical Medicine Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese 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