TGF-β1 → SMAD/p53/USF2 → PAI-1 transcriptional axis in ureteral obstruction-induced renal fibrosis.
TGF-β1 → SMAD/p53/USF2 → PAI-1 transcriptional axis in ureteral obstruction-induced renal fibrosis.
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TGF-β1→SMAD/p53/USF2→PAI-1在输尿管阻塞引起的肾纤维化中的转录轴。
DOI：
10.1007/s00441-011-1181-y
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发表时间：
2012-01
影响因子：
3.6
通讯作者：
Higgins, Paul J.
中科院分区：
文献类型：
--
作者：
Samarakoon, Rohan;Overstreet, Jessica M.;Higgins, Stephen P.;Higgins, Paul J.
慢性肾脏疾病构成了日益增加的医疗负担，仅在美国就有2600万人受到影响。糖尿病、高血压、缺血、急性损伤和泌尿系统梗阻可导致肾纤维化，这是慢性肾脏疾病的常见病理标志。无论病因如何，TGF-β1水平升高与血管紧张素、葡萄糖和氧化应激引发的促纤维化信号通路的激活有关。单侧输尿管梗阻（UUO）是确定肾纤维化进展机制的一个有用且容易获得的模型。纤溶酶原激活物抑制剂-1 （PAI-1）是TGF-β1在几种临床重要纤维化疾病进展中的主要效应物和下游靶点，在UUO中高度上调，与疾病严重程度有因果关系。TGF-β1诱导PAI-1需要SMAD和非SMAD途径（pp60c-src，表皮生长因子受体[EGFR]，丝裂原活化蛋白激酶，p53）。SMAD2/3、pp60c-src、EGFR和p53的激活在阻塞的肾脏中均升高。本文就TGF-β1刺激PAI-1表达在输尿管梗阻肾病进展中的分子基础及翻译意义进行综述。本文讨论的机制似乎适用于其他肾纤维化疾病，并且与组织纤维化的全球问题相关，而不考虑器官部位。
Chronic kidney disease constitutes an increasing medical burden affecting 26 million people in the United States alone. Diabetes, hypertension, ischemia, acute injury, and urological obstruction contribute to renal fibrosis, a common pathological hallmark of chronic kidney disease. Regardless of etiology, elevated TGF-β1 levels are causatively linked to the activation of profibrotic signaling pathways initiated by angiotensin, glucose, and oxidative stress. Unilateral ureteral obstruction (UUO) is a useful and accessible model to identify mechanisms underlying the progression of renal fibrosis. Plasminogen activator inhibitor-1 (PAI-1), a major effector and downstream target of TGF-β1 in the progression of several clinically important fibrotic disorders, is highly up-regulated in UUO and causatively linked to disease severity. SMAD and non-SMAD pathways (pp60c-src, epidermal growth factor receptor [EGFR], mitogen-activated protein kinase, p53) are required for PAI-1 induction by TGF-β1. SMAD2/3, pp60c-src, EGFR, and p53 activation are each increased in the obstructed kidney. This review summarizes the molecular basis and translational significance of TGF-β1-stimulated PAI-1 expression in the progression of kidney disease induced by ureteral obstruction. Mechanisms discussed here appear to be operative in other renal fibrotic disorders and are relevant to the global issue of tissue fibrosis, regardless of organ site.
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DOI：
10.1016/j.jss.2010.06.022
发表时间：
2011-06-01
期刊：
The Journal of surgical research
影响因子：
--
作者：
Asanuma H;Vanderbrink BA;Campbell MT;Hile KL;Zhang H;Meldrum DR;Meldrum KK
通讯作者：
Meldrum KK
影响因子：
6
作者：
Chuang-Tsai, S;Sisson, TH;Simon, RH
通讯作者：
Simon, RH
DOI：
10.1159/000313738
发表时间：
2010-01-01
期刊：
CARDIORENAL SYNDROMES IN CRITICAL CARE
影响因子：
--
作者：
Bonventre, Joseph V.
通讯作者：
Bonventre, Joseph V.
影响因子：
4
作者：
Cho, Hyun-Ji;Kang, Jeong-Han;Chang, Young-Chae
通讯作者：
Chang, Young-Chae
影响因子：
19.6
作者：
Chevalier, RL;Kim, A;Wolstenholme, JT
通讯作者：
Wolstenholme, JT