Cross talk among smad, MAPK, and integrin signaling pathways enhances adventitial fibroblast functions activated by transforming growth factor-β1 and inhibited by gax

被引：32

作者：

Liu, Ping ^{[1
,2
]}

Zhang, Cheng ^{[1
]}

Feng, Jin Bo ^{[1
]}

Zhao, Yu Xia ^{[1
]}

Wang, Xu Ping ^{[1
]}

Yang, Jian Min ^{[1
]}

Zhang, Ming Xiang ^{[1
]}

Wang, Xing Li ^{[3
]}

Zhang, Yun ^{[1
]}

机构：

[1] Shandong Univ, Qilu Hosp, Chinese Minist Educ, Key Lab Cardiovasc Remodeling & Funct Res, Jinan 250012, Shandong, Peoples R China

[2] Shandong Univ, Hosp 2, Jinan 250012, Sgabdibg, Peoples R China

[3] Baylor Coll Med, Michael DeBakey Dept Surg, Div Cardiothorac Surg, St Lukes Episcopal Hosp,Texas Heart Inst, Houston, TX 77030 USA

来源：

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY | 2008年 / 28卷 / 04期

关键词：

adventitial fibroblast; signaling pathway; cell function; TGF-beta; 1; Gax;

D O I：

10.1161/ATVBAHA.107.159889

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective - We investigated whether Smad, mitogen- activated protein kinase (MAPK), and integrin signaling pathways cross-talk to enhance adventitial fibroblast (AF) bioactivity, which was activated by transforming growth factor (TGF)-beta 1 and inhibited by Gax. Methods and Results - Cultured AFs were stimulated with Ad-Gax, TGF-beta 1, and siRNA-Gax. Assays for AFs viabilities demonstrated that TGF-beta 1 and siRNA-Gax enhanced AFs proliferative, migratory, and adherent abilities, whereas Gax counteracted TGF-beta 1-activated actions. Flow cytometry revealed that TGF-beta 1 and siRNA-Gax increased S phase cells; however, Gax decreased AFs in the S phase and increased those in the G0-G1 and apoptotic phases. RT-PCR, Western blotting, and immunocytochemistry showed that TGF-beta 1 and siRNA-Gax upregulated the expression of cytokines in Smad, MAPK, and integrin signaling pathways, and downregulated that of p15, p16, and p21. Conversely, Gax induced downregulation of these cytokines and upregulation of p15, p16, and p21. Thus, these signaling pathways cross-talk to enhance AF bioactivity; Gax effectively counteracts TGF-beta 1 effects, blocks the cross-talk of these pathways, inhibits AF functions, and increases AF apoptosis. Conclusions - Our findings indicate that cross-talk among Smad, MAPK, and integrin signaling pathways may account mainly for the mechanism of AF functions. Gax is a promising therapeutic gene for dissecting the signaling pathways controlling AF bioactivities.

引用

页码：725 / 731

页数：7

共 39 条

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