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无翅型/整合素-1 诱导分泌蛋白-1:肾纤维化的一个新生物标志物。

Wingless/int-1induced secreted protein-1: a new biomarker for renal fibrosis.

机构信息

Department of Nephrology, General Hospital of Ningxia Medical University, Yinchuan, China.

Department of Ultrasonic, General Hospital of Ningxia Medical University, Yinchuan, China.

出版信息

J Biol Regul Homeost Agents. 2021 Jan-Feb;35(1):97-103. doi: 10.23812/20-459-A.

DOI:10.23812/20-459-A
PMID:33480221
Abstract

This study aimed to detect the expression of Wnt-induced secreted protein-1 (WISP-1) in renal fibrosis (RF) and to clarify the underlying mechanism. An in vivo mousee model of unilateral ureteral obstruction (UUO) and in vitro model of fibrosis on renal tubular epithelial NRK52E cells after transforming growth factor-β1 (TGF-β1) stimulation were used. Quantitative real-time PCR (qRT-PCR), Western blot (WB), and immunohistochemistry were used to detect WISP-1 and fibrosis markers, including the expression of fibronectin (FN), collagen I (Col I), collagen IV (Col IV), and α-smooth muscle actin (α-SMA). In vitro experiments showed that the expression of WISP-1 and fibrosis markers FN, Col I, Col IV, and α-SMA in rat renal tubular epithelial cells were significantly higher than that in the control group after 48 h of TGF-β1 stimulation. In vivo experiments showed that the expressions of WISP-1 and fibrosis markers FN, Col I, Col IV, and α-SMA in the obstructed kidney of UUO animal models were significantly increased in mRNA and protein levels compared to normal mice. This study showed that WISP-1 may be an essential cytokine that promotes renal fibrosis, being involved in the development of renal fibrosis.

摘要

本研究旨在检测 Wnt 诱导分泌蛋白-1(WISP-1)在肾纤维化(RF)中的表达,并阐明其潜在机制。采用单侧输尿管梗阻(UUO)的体内小鼠模型和 TGF-β1 刺激后肾管状上皮 NRK52E 细胞纤维化的体外模型。采用定量实时 PCR(qRT-PCR)、Western blot(WB)和免疫组织化学方法检测 WISP-1 和纤维化标志物,包括纤维连接蛋白(FN)、I 型胶原(Col I)、IV 型胶原(Col IV)和α-平滑肌肌动蛋白(α-SMA)的表达。体外实验结果显示,TGF-β1 刺激 48 h 后,大鼠肾小管上皮细胞中 WISP-1 和纤维化标志物 FN、Col I、Col IV 和α-SMA 的表达明显高于对照组。体内实验结果显示,UUO 动物模型梗阻侧肾脏中 WISP-1 和纤维化标志物 FN、Col I、Col IV 和α-SMA 的表达在 mRNA 和蛋白水平均明显增加。本研究表明,WISP-1 可能是促进肾纤维化的重要细胞因子,参与了肾纤维化的发生发展。

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