PD12-08 THE ROLE OF IL-10 IN UNILATERAL URETERAL OBSTRUCTION: REGULATION OF ANGIOGENESIS AND FIBROSIS

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You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder I1 Apr 2017PD12-08 THE ROLE OF IL-10 IN UNILATERAL URETERAL OBSTRUCTION: REGULATION OF ANGIOGENESIS AND FIBROSIS Bethany Desroches, Xinyi Wang, Pu Duann, Meredith Rae, Swathi Balaji, and Sundeep Keswani Bethany DesrochesBethany Desroches More articles by this author , Xinyi WangXinyi Wang More articles by this author , Pu DuannPu Duann More articles by this author , Meredith RaeMeredith Rae More articles by this author , Swathi BalajiSwathi Balaji More articles by this author , and Sundeep KeswaniSundeep Keswani More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.683AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Clinical unilateral ureteral obstruction (UUO) results from pathologies like ureteral calculi, malignancy, trauma, and periureteral fibrosis. UUO requires prompt surgical intervention to prevent progressive inflammation, fibrosis, and kidney function impairment. Novel therapies are needed to recover renal function and architecture after obstruction. Previous reports show the anti-inflammatory cytokine interleukin-10 (IL-10) attenuates fibrosis in a murine model. We and others have shown IL-10 regulates angiogenesis and endothelial progenitor recruitment during dermal and ischemic cardiac tissue repair. We hypothesize that IL-10 can promote angiogenesis and prevent microvascular rarefaction in a murine UUO model. METHODS 8 week-old C57BL/6J (WT) mice and IL-10 null male mice were injected with lenti-IL-10/lenti-GFP (1x1010 IU) under the renal capsule. Three days after injection, UUO was performed. 14 days after UUO, UUO/sham kidneys and serum were collected for RNA, ELISA and immunohistochemical analysis of VEGF and TGFβ isoforms. Primary fibroblasts were isolated from 8-10 week-old male WT mice. IL-10 (50 ng/ml or 200 ng/ml) was added to cultures. VEGF and TGFβ-1 gene expressions were assessed by qPCR at 1, 2, 3 and 6h. Levels of TGFβ-1 and TGFβ-3 were determined at 48h by ELISA. Data presented as mean±SD, n=3/treatment group. P value by ANOVA. RESULTS IL-10 treatment, in vitro, increased VEGF expression (related to physiologic angiogenesis) and altered the expression of TGFβ isoforms (related to pathologic fibrosis). Lenti-Il10 treatment in mice with UUO reduced fibrotic changes between tubules (45±7%, p<0.05) and attenuated tubular dilatation (p<0.05, n=30/group). CD31, an endothelium marker essential to preserving tubular integrity, was normally expressed in healthy kidney parenchyma and decreased after UUO. IL-10 null mice showed a lower basal level of CD31 than WT mice. In both WT and IL-10 null mice, IL-10 treatment preserved CD31, suggesting a role in rescuing integral peritubular capillaries. CONCLUSIONS Ureteral obstruction can cause remodeled renal architecture and decrease in renal function. Our results in a murine UUO model show that IL-10 can effectively promote angiogenesis in vitro and prevent microvascular rarefaction in vivo. Mice treated with IL-10 show decreased fibrotic change and increased markers for tubular integrity. These results from the in vivo studies of UUO, and the in vitro studies of IL-10′s influence in angiogenesis and fibrosis of the kidney, may lead to novel treatments for the sequelae of urinary tract obstruction. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e268 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Bethany Desroches More articles by this author Xinyi Wang More articles by this author Pu Duann More articles by this author Meredith Rae More articles by this author Swathi Balaji More articles by this author Sundeep Keswani More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...