Surfactant protein A deficiency exacerbates renal interstitial fibrosis following obstructive injury in mice.
Surfactant protein A deficiency exacerbates renal interstitial fibrosis following obstructive injury in mice.
复制标题
表面活性剂蛋白 A 缺乏会加剧小鼠阻塞性损伤后的肾间质纤维化。
DOI：
10.1016/j.bbadis.2016.11.032
复制
发表时间：
2017-02
影响因子：
6.2
通讯作者：
Chen, Shi-You
中科院分区：
文献类型：
--
作者：
Tian, Shaojiang;Li, Chenxiao;Ran, Ran;Chen, Shi-You
关键词：
肾间质纤维化是几乎所有类型的慢性肾脏疾病的不可避免的后果。然而，其潜在机制尚未完全了解。在本研究中，我们确定了表面活性蛋白A（SP-A）作为一种新的蛋白因子参与单侧输尿管梗阻（UUO）引起的肾纤维化。UUO诱导小鼠肾上皮中SP-A表达，可能是由于酸性应激和炎症增加。有趣的是，SP-A缺乏加重了UUO引起的肾脏结构损伤、巨噬细胞积聚和肾小管间质纤维化。SP-A缺乏似乎通过增强间质肌成纤维细胞积聚而使纤维化恶化。此外，SP-A缺乏增加了TGF-β1的表达，TGF-β1是肾纤维化的主要调节因子，特别是在间质细胞中。从机制上讲，SP-A缺乏增加了高迁移率族蛋白1（HMGB 1）的表达和释放，HMGB 1是一种调节TGF-β表达/信号传导的因子，与肾纤维化有关。SP-A还阻断了HMGB 1诱导TGF-β1表达和从肾成纤维细胞转分化为肌成纤维细胞的活性，表明SP-A通过阻断HMGB 1的表达和纤维化功能来保护肾脏。由于SP-A在体外和体内肾组织中与HMGB 1发生物理相互作用，SP-A可能通过与HMGB 1结合，从而在UUO诱导的肾纤维化过程中滴定其活性，从而发挥其保护作用。
Renal interstitial fibrosis is an inevitable consequence of virtually every type of chronic kidney disease. The underlying mechanisms, however, are not completely understood. In the present study, we identified surfactant protein A (SP-A) as a novel protein factor involved in the renal fibrosis induced by unilateral ureter obstruction (UUO). UUO induced SP-A expression in mouse kidney epithelium, likely due to the increased acidic stress and inflammation. Interestingly, SP-A deficiency aggravated UUO-prompted kidney structural damage, macrophage accumulation, and tubulointerstitial fibrosis. SP-A deficiency appeared to worsen the fibrosis by enhancing interstitial myofibroblast accumulation. Moreover, SP-A deficiency increased the expression of TGF-β1, the major regulator of kidney fibrosis, particularly in the interstitial cells. Mechanistically, SP-A deficiency increased the expression and release of high mobility group box 1 (HMGB1), a factor regulating TGF-β expression/signaling and implicated in renal fibrosis. SP-A also blocked HMGB1 activities in inducing TGF-β1 expression and myofibroblast transdifferentiation from kidney fibroblasts, demonstrating that SP-A protects kidney by impeding both the expression and fibrogenic function of HMGB1. Since SP-A physically interacted with HMGB1 both in vitro and in kidney tissue in vivo, SP-A may exert its protective role by binding to HMGB1 and thus titrating its activity during UUO-induced renal fibrosis.
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DOI：
10.1097/shk.0000000000000270
发表时间：
2015-01
期刊：
Shock (Augusta, Ga.)
影响因子：
--
作者：
Liu J;Abdel-Razek O;Liu Z;Hu F;Zhou Q;Cooney RN;Wang G
通讯作者：
Wang G
DOI：
10.1165/rcmb.2002-0274oc
发表时间：
2003-11-01
影响因子：
6.4
作者：
Madsen, J;Tornoe, I;Holmskov, U
通讯作者：
Holmskov, U
影响因子：
2.6
作者：
Lee, HM;Kang, HJ;Hwang, SJ
通讯作者：
Hwang, SJ
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。
影响因子：
3.6
作者：
Samarakoon, Rohan;Overstreet, Jessica M.;Higgins, Stephen P.;Higgins, Paul J.
通讯作者：
Higgins, Paul J.
影响因子：
13.6
作者：
Lee, Sik;Huen, Sarah;Cantley, Lloyd G.
通讯作者：
Cantley, Lloyd G.