The role of microRNA-101a and cycloxygenase-2 in kidney damage induced by hyperuricemia
1.Department of Nephrology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325027; 2.Department of Endocrinology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325027
YE Hanyang1,JIN Jian2,LI Zhanyuan1, et al. The role of microRNA-101a and cycloxygenase-2 in kidney damage induced by hyperuricemia[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2015, 45(4): 256-.
Abstract:Objective: To investigate the effects of miR-101a and cycloxygenase-2 (COX-2) on rats model of urate nephropathy. Methods: Twenty four rats models of urate nephropathy through fed with yeast and adenine for 21 days were divided into three groups, normal control groups, model groups and celecoxib groups. Serum creatinine (Cr), blood urea nitrogen (BUN) and blood uric acid (UA) was tested after feeding with yeast and adenine for 21 days. The real time PCR was preformed to analyze the expression of miR-101a and Western Blot was preformed to analyze the expression of COX-2 and caspase-3 in renal cortex. Results: Cr, BUN and UA of model group were significantly higher than that of normal control groups (P<0.05). The expression of miR-101a in renal cortex from model groups was lower than that of normal control groups (P<0.05), while higher than that of celecoxib groups (P<0.05). The expression of COX2 and caspase-3 in renal cortex from model groups were higher than that of normal control group (P<0.05), while lower than that of celecoxib groups (P<0.05). Conclusion: Decreasing miR-101a and increasing COX2 may involve in kidney damage induced by hyperuricemia, celecoxib as a specific inhibitor protects kidney from this damage.
[1] Weinberg JB. Nitric oxide synthase 2 and cyclooxygenase 2 interactions in inflammation[J]. Immunol Res, 2000, 22(2-3): 319-341.
[2] Harper KA, Tyson-Capper AJ. Complexity of COX-2 gene regulation[J]. Biochem Soc Trans, 2008, 36(Pt 3): 543-545.
[3] Strillacci A, Griffoni C, Sansone P, et al. MiR-101 downregulation is involved in cyclooxygenase-2 overexpression in human colon cancer cells[J]. Exp Cell Res, 2009, 315(8): 1439-1447.
[4] 何立群, 聂永红, 邹士林, 新型尿酸性肾病动物模型的建 立[J]. 上海实验动物科学, 2001, 21(1): 22-24.
[5] Diwan V, Mistry A, Gobe G, et al. Adenine-induced chronic kidney and cardiovascular damage in rats[J]. J Pharmacol Toxicol Methods, 2013, 68(2): 197-207.
[6] Lobo JC, Stockler-Pinto MB, da Nóbrega AC, et al. Is there association between uric acid and inflammation in hemodialysis patients?[J]. Ren Fail, 2013, 35(3): 361-366.
[7] Mitchell JA,Warner TD. Cyclo-oxygenase-2: pharmacology, physiology, biochemistry and relevance to NSAID therapy[J]. Br J Pharmacol, 1999, 128(6): 1121-1132.
[8] Ranganathan PV, Jayakumar C, Mohamed R, et al. Netrin-1 regulates the inflammatory response of neutrophils and macrophages, and suppresses ischemic acute kidney injury by inhibiting COX-2-mediated PGE2 production[J]. Kidney Int, 2013, 83(6): 1087-1098.
[9] Nicholas K, Melissa C, Eliana GV, et al. Identification of the molecular pathways that drive constitutive renal COX-2 expression: implications for novel COX-2-targetted therapies that spare the cardiovascular system[J]. The FASEB Journal, 2014, 28(1): 837-839.
[10] Convento MS, Pessoa E, Dalboni MA, et al. Pro-inflammatory and oxidative effects of noncrystalline uric acid in human mesangial cells: contribution to hyperuricemic glomerular damage[J]. Urol Res, 2011, 39(1): 21-27.
[11] Chakrabarty A, Tranguch S, Daikoku T, et al. MicroRNA regulation of cyclooxygenase-2 during embryo implantation
[J]. Proc Natl Acad Sci USA, 2007, 104(38): 15144-15149.
[12] Wang HJ, Ruan HJ, He XJ, et al. MicroRNA-101 is down-regulated in gastric cancer and involved in cell migration and invasion [J]. Eur J Cancer, 2010, 46(12): 2295-2303.
[13] Tanaka T, Haneda S, Imakawa K, et al. A microRNA, miR-101a, controls mammary gland development by regulating cyclooxygenase-2 expression[J]. Differentiation, 2009, 77(2): 181-187.