Profiling of anti-fibrotic signaling by hepatocyte growth factor in renal fibroblasts
Profiling of anti-fibrotic signaling by hepatocyte growth factor in renal fibroblasts
复制标题
DOI：
10.1016/j.bbrc.2009.05.010
复制
发表时间：
2009-07-17
影响因子：
3.1
通讯作者：
Odenthal, Margarete
中科院分区：
文献类型：
--
作者：
Schievenbusch, Stephanie;Strack, Ingo;Odenthal, Margarete
肝细胞生长因子（HGF）是一种影响细胞增殖和分化的多功能生长因子。由于其促有丝分裂潜力，HGF在急性肾损伤后的肾小管修复和再生中起重要作用。然而，最近的报道表明，HGF也作为一种抗炎和抗纤维化因子，影响各种类型的细胞，如肾成纤维细胞和触发肾小管间质纤维化的kidney.The本研究提供的证据表明，HGF刺激肾成纤维细胞的结果在Erk 1/2和Akt途径的激活。如前所述，Erk 1/2磷酸化导致Smad-连接子磷酸化，从而拮抗TGF β诱导的细胞信号。然而，通过siRNA介导的ErK 1/2-Smad连接的沉默，我们现在证明Akt信号传导作为负责HGF抗纤维化作用的辅助途径。为了确定HGF的抗纤维化功能，我们通过微阵列杂交对HGF刺激的肾成纤维细胞进行了全面的表达谱分析。功能聚类分析和定量PCR分析表明，HGF刺激的途径通过减少细胞外基质蛋白、各种趋化因子和CCN家族成员的表达来转移肾间质成纤维细胞中的抗纤维化作用。(C)2009 Elsevier Inc. All rights reserved.
Hepatocyte growth factor (HGF) is a multifunctional growth factor affecting cell proliferation and differentiation. Due to its mitogenic potential, HGF plays an important role in tubular repair and regeneration after acute renal injury. However, recent reports have shown that HGF also acts as an anti-inflammatory and anti-fibrotic factor, affecting various cell types such as renal fibroblasts and triggering tubulointerstitial fibrosis of the kidney.The present study provides evidence that HGF stimulation of renal fibroblasts results in the activation of both the Erk1/2 and the Akt pathways. As previously shown, Erk1/2 phosphorylation results in Smad-linker phosphorylation, thereby antagonizing cellular signals induced by TGF beta. By siRNA mediated silencing of the ErK1/2-Smad linkage, however, we now demonstrate that Akt signaling acts as an auxiliary pathway responsible for the anti-fibrotic effects of HGF. In order to define the anti-fibrotic function of HGF we performed comprehensive expression profiling of HGF-stimulated renal fibroblasts by microarray hybridization. Functional cluster analyses and quantitative PCR assays indicate that the HGF-stimulated pathways transfer the anti-fibrotic effects in renal interstitial fibroblasts by reducing expression of extracellular matrix proteins, various chemokines, and members of the CCN family. (C) 2009 Elsevier Inc. All rights reserved.