Background: Uric acid (UA) plays important roles in inducing renal inflammation, intra-renal vasoconstriction and renal\ndamage. Endothelin-1 (ET-1) is a well-known profibrotic factor in the kidney and is associated with fibroblast expansion.\nWe examined the role of hyperuricemia conditions in causing elevation of ET-1 expression and kidney injury.\nMethods: Hyperuricemia was induced in mice using daily intraperitoneal injection of uric acid 125 mg/Kg body\nweight. An NaCl injection was used in control mice. Mice were euthanized on days-7 (UA7) and 14 (UA14). We also\nadded allopurinol groups (UAL7 and UAL14) with supplementation of allopurinol 50 mg/Kg body weight orally. Uric\nacid and creatinine serum were measured from blood serum. Periodic Acid Schiff (PAS) and Sirius Red staining were\ndone for glomerulosclerosis, tubular injury and fibrosis quantification. mRNA expression examination was performed for\nnephrin, podocin, preproEndothelin-1 (ppET-1), MCP-1 and ICAM-1. PDGFR�² immunostaining was done for\nquantification of fibroblast, while �±-SMA immunostaining was done for localizing myofibroblast. Western blot analysis\nwas conducted to quantify TGF-�²1, �±-SMA and Endothelin A Receptor (ETAR) protein expression.\nResults: Uric acid and creatinine levels were elevated after 7 and 14 days and followed by significant increase of\nglomerulosclerosis and tubular injury score in the uric acid group (p < 0.05 vs. control). Both UA7 and UA14 groups had\nhigher fibrosis, tubular injury and glomerulosclerosis with significant increase of fibroblast cell number compared with\ncontrol. RT-PCR revealed down-regulation of nephrin and podocin [removed]p < 0.05 vs. control), and up-regulation of\nMCP-1, ET-1 and ICAM-1 [removed]p < 0.05 vs. control). Western blot revealed higher expression of TGF-�²1 and �±-SMA\nprotein expression. Determination of allopurinol attenuated kidney injury was based on reduction of fibroblast cell\nnumber, inflammation mediators and ppET-1 expression with reduction of TGF-�²1 and �±-SMA protein expression.\nConclusions: UA induced glomerulosclerosis, tubular injury and renal fibrosis with reduction of podocyte function and\ninflammatory mediator elevation. ET-1 and fibroblast expansion might modulate hyperuricemia induced renal fibrosis.
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