Honokiol ameliorates renal fibrosis by inhibiting extracellular matrix and pro-inflammatory factors in vivo and in vitro
Honokiol ameliorates renal fibrosis by inhibiting extracellular matrix and pro-inflammatory factors in vivo and in vitro
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DOI：
10.1111/j.1476-5381.2011.01242.x
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发表时间：
2011-06-01
影响因子：
7.3
通讯作者：
Liu, Shing-Hwa
中科院分区：
文献类型：
--
作者：
Chiang, Chih-Kang;Sheu, Meei-Ling;Liu, Shing-Hwa
背景与展望肾纤维化是导致终末期肾病发展的共同途径。本研究调查，在体内和体外，抗纤维化和抗炎作用，特别是对肾小管细胞的上皮间质转化，施加和厚朴，传统医学中使用的植物化学物质，和这些effects. EXPERIMENTARY APPROACH抗纤维化作用在体内进行了测定，在大鼠模型肾纤维化[单侧输尿管梗阻（UUO）模型]。大鼠肾小管上皮细胞系（NRK-52 E）刺激转化生长因子-β 1（TGF-β 1）和治疗与honoklavine，以探讨这些抗纤维化作用的可能机制。通过北方或Western印迹分析基因或蛋白质表达。利用结缔组织生长因子（CTGF）启动子驱动的荧光素酶活性研究转录调控。关键词TSH能在体内和体外减缓肾纤维化的发展。和厚朴治疗减弱了UUO模型中肾小管间质纤维化和促纤维化因子的表达。和诺平还降低了趋化因子CCL 2和细胞内粘附分子-1的mRNA表达，以及UUO肾脏中I型（α 1）胶原和纤连蛋白的积累。TGF-β 1和CTGF荧光素酶活性诱导的Smad-2/3磷酸化在肾小管cells中也被honoklastin.CONCLUSIONS AND IMPLICATIONSHonoklastin抑制促纤维化和促炎症因子和细胞外基质蛋白的表达。和厚朴酚可能成为预防肾纤维化的治疗剂。
BACKGROUND AND PURPOSERenal fibrosis acts as the common pathway leading to the development of end-stage renal disease. The present study investigated, in vivo and in vitro, the anti-fibrotic and anti-inflammatory effects, particularly on the epithelial to mesenchymal transition of renal tubular cells, exerted by honokiol, a phytochemical used in traditional medicine, and mechanisms underlying these effects.EXPERIMENTAL APPROACHAnti-fibrotic effects in vivo were assayed in a rat model of renal fibrosis [the unilateral ureteral obstruction (UUO) model]. A rat tubular epithelial cell line (NRK-52E) was stimulated by transforming growth factor-beta 1 (TGF-beta 1) and treated with honokiol to explore possible mechanisms of these anti-fibrotic effects. Gene or protein expression was analysed by Northern or Western blotting. Transcriptional regulation was investigated using luciferase activity driven by a connective tissue growth factor (CTGF) promoter.KEY RESULTSHonokiol slowed development of renal fibrosis both in vivo and in vitro. Honokiol treatment attenuated tubulointerstitial fibrosis and expression of pro-fibrotic factors in the UUO model. Honokiol also decreased expression of the mRNA for the chemokine CCL2 and for the intracellular adhesion molecule-1, as well as accumulation of type I (alpha 1) collagen and fibronectin in UUO kidneys. Phosphorylation of Smad-2/3 induced by TGF-beta 1 and CTGF luciferase activity in renal tubular cells were also inhibited by honokiol.CONCLUSIONS AND IMPLICATIONSHonokiol suppressed expression of pro-fibrotic and pro-inflammatory factors and of extracellular matrix proteins. Honokiol may become a therapeutic agent to prevent renal fibrosis.