Peroxiredoxin 1 inhibits the oxidative stress induced apoptosis in renal tubulointerstitial fibrosis
Peroxiredoxin 1 inhibits the oxidative stress induced apoptosis in renal tubulointerstitial fibrosis
复制标题
Peroxiredoxin 1 抑制肾小管间质纤维化中氧化应激诱导的细胞凋亡。
DOI：
10.1111/nep.12515
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发表时间：
2015-11-01
期刊：
影响因子：
2.5
通讯作者：
Tao, Lijian
中科院分区：
文献类型：
--
作者：
Mei, Wenjuan;Peng, Zhangzhe;Tao, Lijian
目的细胞凋亡是肾小管间质纤维化的重要机制之一。我们确定了蛋白过氧化物酶1（Prx 1）在保护肾小管上皮细胞发生凋亡的大鼠和人kidney.MethodsImmunohistochemistry（IHC）染色法检测Prx 1在单侧输尿管梗阻（UUO）大鼠和梗阻性肾病患者的肾脏中的表达。在NRK-52 E（大鼠肾小管上皮细胞系）细胞中进行了通过抑制siRNA和过表达质粒方法对Prx 1表达的调节。结果免疫组织化学染色显示Prx 1在UUO大鼠肾脏中表达于肾小管上皮细胞胞浆中。通过IHC和实时聚合酶链反应证实了UUO大鼠肾小管间质纤维化过程中Prx 1的减少，并伴随着TUNEL阳性细胞的升高。氟非尼酮（AKF-PD），一种新的抗肾小管间质纤维化药物，减弱了UUO大鼠Prx 1的减少。过氧化氢（H2 O2）诱导的氧化应激激活p38 MAPK，诱导NRK-52 E细胞凋亡; Prx 1的敲低可使NRK-52 E细胞的上述两种作用敏感，而Prx 1的过表达可抑制NRK-52 E细胞的凋亡和p38的磷酸化。Prx 1可能通过抑制p38 MAPK通路抑制H2 O2诱导的细胞凋亡而减轻其发病机制。Prx 1可能是一个有用的靶点，用于保护性治疗肾小管间质纤维化。利用标准的大鼠单侧输尿管梗阻模型，显示抗氧化酶过氧化物酶1（Prx 1）的表达和分布。他们随后的研究表明，氟非尼酮治疗通过维持PRx 1从而抑制细胞凋亡来改善进展。
AimApoptosis is one of the most important mechanisms underlying renal tubulointerstitial fibrosis. We identified a role of protein Peroxiredoxin 1 (Prx1) in protecting apoptosis occurred in tubular epithelial cells of the rat and human kidney.MethodsImmunohistochemistry (IHC) staining was used to detect Prx1 expression in kidney derived from unilateral-ureteral obstruction (UUO) rats or patients with obstructive nephropathy. Modulation of Prx1 expression by transfecting siRNA and overexpression plasmid approach were carried out in NRK-52E (rat kidney tubular epithelial cell line) cells. UUO-induced apoptosis was determined using TUNEL assay.ResultsImmunohistochemistry staining showed that Prx1 expressed in the cytoplasm of renal tubular epithelial cells, in the kidneys of UUO rats. The reduction was confirmed by both IHC and real-time polymerase chain reaction following a course of renal tubulointerstitial fibrosis in UUO rats and a decrease of Prx1 occurred concomitantly with an elevation of TUNEL-positive cells. Fluorofenidone (AKF-PD), a new anti-tubulointerstitial fibrotic agent, attenuated Prx1 reduction in UUO rats. Furthermore, hydrogen peroxide (H2O2)-derived oxidative stress activated p38 MAPK, and induced apoptosis in NRK-52E cells; knockdown of Prx1 sensitized both events in NRK-52E cells, and overexpression of Prx1 diminished the apoptosis and the phosphorylation of p38ConclusionDownregulation of Prx1 occurred in renal tubular epithelial cells of UUO rats and patients with obstructive nephropathy. Prx1 may alleviate the pathogenesis by inhibiting H2O2-induced apoptosis via inhibiting the p38 MAPK pathway. Prx1 may represent a useful target for a protective therapy towards renal tubulointerstitial fibrosis.Summary at a Glance Mei etal. utilize the standard rat model of unilateral ureteric obstruction model to demonstrate the expression and distribution of the antioxidant enzyme peroxiredoxin 1 (Prx1). Their subsequent studies suggest that fluorofenidone treatment ameliorates progression through maintaining PRx1, and thereby inhibiting apoptosis.