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Thus, we hypothesized that treatment with a selective inhibition of HuR function with a small molecule, KH-3, would down-regulate HuR-targeted proinflammatory transcripts thereby improving glomerulosclerosis in experimental nephritis, where glomerular cellular HuR is elevated. Three experimental groups included normal and diseased rats treated with or without KH-3. Disease was induced by the monoclonal anti-Thy 1.1 antibody. KH-3 was given via daily intraperitoneal injection from day 1 after disease induction to day 5 at the dose of 50 mg\/kg BW\/day. At day 6, diseased animals treated with KH-3 showed significant reduction in glomerular HuR levels, proteinuria, podocyte injury determined by ameliorated podocyte loss and podocin expression, glomerular staining for periodic acid-Schiff positive extracellular matrix proteins, fibronectin and collagen IV and mRNA and protein levels of profibrotic markers, compared with untreated disease rats. KH-3 treatment also reduced disease-induced increases in renal TGF\u03b21 and PAI-1 transcripts. Additionally, a marked increase in renal NF-\u03baB-p65, Nox4, and glomerular macrophage cell infiltration observed in disease control group was largely reversed by KH-3 treatment. These results strongly support our hypothesis that down-regulation of HuR function with KH-3 has therapeutic potential for reversing glomerulosclerosis by reducing abundance of pro-inflammatory transcripts and related inflammation.<\/jats:p>","DOI":"10.1042\/cs20200193","type":"journal-article","created":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T10:31:13Z","timestamp":1591007473000},"page":"1433-1448","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Inhibition of RNA-binding protein HuR reduces glomerulosclerosis in experimental nephritis"],"prefix":"10.1042","volume":"134","author":[{"given":"Simeng","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology and Hypertension, University of Utah Health Science, Salt Lake City, UT, U.S.A."},{"name":"Department of Internal Medicine, Division of Nephrology, Nanjing Medical University Jiangsu Province Hospital, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhimin","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology and Hypertension, University of Utah Health Science, Salt Lake City, UT, U.S.A."},{"name":"Department of Internal Medicine, Division of Nephrology, Nanjing Medical University Jiangsu Province Hospital, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology and Hypertension, University of Utah Health Science, Salt Lake City, UT, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, University of Kansas, Lawrence, KS, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Aube","sequence":"additional","affiliation":[{"name":"Department of Chemical Biology and Medical Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, University of Kansas, Lawrence, KS, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changying","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, Nanjing Medical University Jiangsu Province Hospital, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9186-5269","authenticated-orcid":false,"given":"Yufeng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology and Hypertension, University of Utah Health Science, Salt Lake City, UT, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2020,6,18]]},"reference":[{"key":"2021113011124204300_B1","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1159\/000493278","article-title":"Inflammation in Diabetic Kidney Disease","volume":"143","author":"Perez-Morales","year":"2019","journal-title":"Nephron"},{"key":"2021113011124204300_B2","doi-asserted-by":"publisher","first-page":"2180373","DOI":"10.1155\/2018\/2180373","article-title":"Inflammation-Related Mechanisms in Chronic Kidney Disease Prediction, Progression, and Outcome","volume":"2018","author":"Mihai","year":"2018","journal-title":"J. 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