MP44-10 HIGH MOLECULAR WEIGHT HYALURONAN ATTENUATES SCARRING IN ACUTE KIDNEY INJURY

Abstract

You have accessJournal of UrologyPediatric Urology II (MP44)1 Sep 2021MP44-10 HIGH MOLECULAR WEIGHT HYALURONAN ATTENUATES SCARRING IN ACUTE KIDNEY INJURY Pratik Kanabur, Aditya Kaul, Scott Manson, Swathi Balaji, Paul Austin, Sandeep Keswani, and Xinyi Wang Pratik KanaburPratik Kanabur More articles by this author , Aditya KaulAditya Kaul More articles by this author , Scott MansonScott Manson More articles by this author , Swathi BalajiSwathi Balaji More articles by this author , Paul AustinPaul Austin More articles by this author , Sandeep KeswaniSandeep Keswani More articles by this author , and Xinyi WangXinyi Wang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002065.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Renal fibrosis induces morbidity in pediatric patients, which can persist into adulthood. Hyaluronan (HA), a major extracellular matrix component, regulates fibrosis based on its molecular weight (MW). We have reported that IL-10 upregulates high MW-HA synthesis via fibroblasts to attenuate fibrosis in a chronic kidney disease model. However, the effect of high MW-HA in acute kidney injury is unknown. Our data suggests that HA is upregulated in epithelial tubular cells in an acute kidney injury model. We hypothesize that tubular cell-specific high MW-HA reduces fibrosis caused by acute kidney injury. METHODS: We performed unilateral ischemia/reperfusion(I/R) on C57BL/6J male mice treated with and without IL-10 and also with and without 4-methylumbelliferone(4MU), an HA inhibitor. I/R or sham kidneys were collected at Day 3, 7, and 14 for the levels of HA synthases(HAS1-3) and hyaluronidases(HYAL1-2) by qPCR, total HA by ELISA, and fibrosis outcome and tubular cell proliferation by immunohistochemistry. In vitro studies were also done with human proximal tubular HK-2 cells, which were used to determine the effect of IL-10 on HA enzymes with/without TGFβ, which mimics the fibrotic phenotype. ANOVA and Student’s t-test were used as appropriate with statistical significance defined as p<0.05. RESULTS: I/R significantly increases HA production with the peak of enzyme production at day 3. With IL-10 treatment, we observe upregulated total HA at D3&D7, increased tubular cell proliferation, and reduced fibrosis. These effects however are not observed when HA is inhibited by 4-MU. In vitro, TGFβ significantly alters expression of HAS1&3 and HYAL1 compared to control, and IL-10 treatment increases HA and restores HAS1 level compared to control (all p<0.05) CONCLUSIONS: Tubular-specific HA plays a protective role in response to acute renal injury, and the upregulation of HA by IL-10 can attenuate fibrosis. We identified a previously unreported role for high MW-HA that occurs in response to kidney injury. We also elucidated the mechanisms underlying HA-attenuated fibrosis to inspire novel therapeutics. Source of Funding: N/A © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e796-e796 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Pratik Kanabur More articles by this author Aditya Kaul More articles by this author Scott Manson More articles by this author Swathi Balaji More articles by this author Paul Austin More articles by this author Sandeep Keswani More articles by this author Xinyi Wang More articles by this author Expand All Advertisement Loading ...