Jiang Ling, Chen Xiu-Ping, Long Yao-Bin, Lei Feng-Ying, Zhou Zhi-Qiang, Qin Yuan-Han, Huang Wei-Fang, Zhou Tian-Biao
a Department of Pediatrics , The First Affiliated Hospital of GuangXi Medical University , Nanning , China and.
b Department of Nephrology , The Six Affiliated Hospital of Sun Yat-Sen University , Guangzhou , China.
J Recept Signal Transduct Res. 2015;35(4):258-68. doi: 10.3109/10799893.2014.975249. Epub 2014 Oct 31.
Peroxisome proliferator-activated receptorγ (PPARγ) can regulate the process of cell apoptosis and is related to the progression of renal disorders. Retinoic acid receptor alpha (RARα) is one of the nuclear receptors involved in a variety of kidney diseases. Renal interstitial fibrosis (RIF) is a common denominator of chronic kidney disease (CKD). This study investigated whether a potential signaling pathway existed between PPARγ and RARα in RIF rats with unilateral ureteral obstruction (UUO). The rats were randomly divided into four groups: a model group subjected to UUO (GU), and three other groups treated with rosiglitazone sodium (GRS), GW9662 and dimethyl sulfoxide (DMSO), n = 40, respectively. Renal tissues were collected two and four weeks after post-surgery. The relevant indicators were detected. In comparison with the GU group, the expressions of PPARγ and RARα (protein and mRNA) were increased in the GRS group, and decreased in the GW9662 group (all p < 0.01). The RIF index, mRNA and protein expression of transforming growth factor-β1 (TGF-β1), and the protein expressions of collagen-IV (Col-IV) and fibronectin (FN) in the GRS group were more markedly reduced than those in the GU group; their levels in the GW9662 group were elevated (all p < 0.01). PPARγ or RARα was negatively correlated to the RIF index, TGF-β1, Col-IV and FN. PPARγ was positively correlated with RARα (all p < 0.01). In conclusion, PPARγ agonist can elevate the expression of PPARγ or RARα in RIF rats. There might be a potential signaling pathway between PPARγ and RARα in RIF disease.
过氧化物酶体增殖物激活受体γ（PPARγ）可调节细胞凋亡过程，并与肾脏疾病的进展相关。维甲酸受体α（RARα）是参与多种肾脏疾病的核受体之一。肾间质纤维化（RIF）是慢性肾脏病（CKD）的一个共同特征。本研究调查了单侧输尿管梗阻（UUO）所致RIF大鼠中PPARγ与RARα之间是否存在潜在的信号通路。大鼠被随机分为四组：接受UUO的模型组（GU），以及分别用罗格列酮钠（GRS）、GW9662和二甲基亚砜（DMSO）处理的其他三组，每组n = 40。术后两周和四周收集肾脏组织。检测相关指标。与GU组相比，GRS组中PPARγ和RARα的表达（蛋白质和mRNA）升高，而GW9662组中则降低（均p < 0.01）。GRS组的RIF指数、转化生长因子-β1（TGF-β1）的mRNA和蛋白质表达，以及IV型胶原（Col-IV）和纤连蛋白（FN）的蛋白质表达比GU组更显著降低；它们在GW9662组中的水平升高（均p < 0.01）。PPARγ或RARα与RIF指数、TGF-β1、Col-IV和FN呈负相关。PPARγ与RARα呈正相关（均p < 0.01）。总之，PPARγ激动剂可提高RIF大鼠中PPARγ或RARα的表达。在RIF疾病中，PPARγ与RARα之间可能存在潜在的信号通路。
