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We aimed at investigating whether alteration of miR-194-dependent MMPs and PARP-1 causes renal fibrosis in diabetes kidney, and whether H<jats:sub>2<\/jats:sub>S ameliorates fibrosis. Wild type, diabetic Akita mice as well as mouse glomerular endothelial cells (MGECs) were used as experimental models, and GYY4137 as H<jats:sub>2<\/jats:sub>S donor. In diabetic mice, plasma H<jats:sub>2<\/jats:sub>S levels were decreased while ROS and expression of its modulator (ROMO1) were increased. In addition, alteration of MMPs-9, \u221213 and \u221214 expression, PARP-1, HIF1\u03b1, and increased collagen biosynthesis as well as collagen cross-linking protein, P4HA1 and PLOD2 were observed along with diminished vascular density in diabetic kidney. These changes were ameliorated by GYY4137. Further, downregulated miRNA-194 was normalized by GYY4137 in diabetic kidney. Similar results were obtained in <jats:italic>in vitro<\/jats:italic> condition. Interestingly, miR-194 mimic also diminished ROS production, and normalized ROMO1, MMPs-9, \u221213 and \u221214, and PARP-1 along with collagen biosynthesis and cross-linking protein in HG condition. We conclude that decrease H<jats:sub>2<\/jats:sub>S diminishes miR-194, induces collagen deposition and realignment leading to fibrosis and renovascular constriction in diabetes. GYY4137 mitigates renal fibrosis in diabetes through miR-194-dependent pathway.<\/jats:p>","DOI":"10.1038\/s41598-017-11256-3","type":"journal-article","created":{"date-parts":[[2017,9,1]],"date-time":"2017-09-01T14:43:13Z","timestamp":1504276993000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["GYY4137, a Hydrogen Sulfide Donor Modulates miR194-Dependent Collagen Realignment in Diabetic Kidney"],"prefix":"10.1038","volume":"7","author":[{"given":"AM Sashi Papu","family":"John","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sourav","family":"Kundu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sathnur","family":"Pushpakumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maura","family":"Fordham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manas","family":"Mukhopadhyay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Utpal","family":"Sen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,9,7]]},"reference":[{"key":"11256_CR1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0134946","volume":"10","author":"JF Lensen","year":"2015","unstructured":"Lensen, J. 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