TWEAK通过P38MAPK途径促进大鼠心肌成纤维细胞Ⅰ型胶原和MMP-1的表达

山东大学学报(医学版) ›› 2012, Vol. 50 ›› Issue (11): 43-47.

TWEAK通过P38MAPK途径促进大鼠心肌成纤维细胞Ⅰ型胶原和MMP-1的表达

王其磊1，任满意2，王德金1，徐冬玲1，杜贻萌1，王旭平3，隋树建1

1.山东大学第二医院心内科，济南 250033； 2.山东省胸科医院心内科，济南 250133
3.山东大学齐鲁医院心内科，教育部和卫生部心血管重构与功能重点研究实验室，济南 250012

收稿日期:2012-03-29 出版日期:2012-11-10 发布日期:2012-11-10
通讯作者: 隋树建(1960- )，男，教授，博士生导师，主要从事高血压病与冠心病的基础和临床研究。 E-mail:suisj@163.com
作者简介:王其磊(1985- )，男，硕士研究生，主要从事高血压与心肌纤维化的研究。
基金资助:
山东省科技攻关计划(2007GG10002014)。

TWEAK promotes expressions of collagen I and matrix metalloproteinase1
in rat cardiac fibroblasts via P38MAPK pathway

WANG Qi-lei1, REN Man-yi2, WANG De-jin1, XU Dong-ling1,
DU Yi-meng1, WANG Xu-ping3, SUI Shu-jian1

1. Department of Cardiology， the Second Hospital of Shandong University, Jinan 250033, China;
2. Department of Cardiology, Shandong Provincial Chest Hospital, Jinan 250133, China;
3． Department of Cardiology, Qilu Hospital of Shandong University, Key Laboratory of Cardiovascular Remodeling and
Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Jinan 250012, China

Received:2012-03-29 Online:2012-11-10 Published:2012-11-10

摘要/Abstract

摘要：

目的探讨肿瘤坏死因子样凋亡微弱诱导剂(TWEAK)影响心肌成纤维细胞(CFs)中Ⅰ型胶原和基质金属蛋白酶1(MMP-1)表达的作用机制。方法取Wistar新生大鼠CFs,加入重组人TWEAK(rhTWEAK)及P38MAPK抑制剂(SB203580)干预,将实验分为① 对照组：不加干预因素；② TWEAK组：加入100ng/mL TWEAK；③ TWEAK+SB203580组：加入100ng/mLTWEAK+SB203580。采用MTT法检测CFs增殖；Western blot法检测Ⅰ型胶原蛋白及磷酸化P38MAPK(P-P38MAPK)蛋白表达；qRT-PCR法检测Ⅰ型胶原mRNA表达；ELISA法检测CFs细胞培养液中MMP-1的浓度。结果加入TWEAK干预后，促进了CFs增殖，Ⅰ型胶原蛋白及P-P38MAPK蛋白表达上调，Ⅰ型胶原mRNA和MMP-1 表达上调。加入SB203580可抑制CFs增殖，部分抑制Ⅰ型胶原mRNA、Ⅰ型胶原蛋白、P-P38MAPK蛋白及MMP-1的表达。结论 TWEAK可通过P38MAPK途径促进CFs 表达Ⅰ型胶原和MMP1。

关键词: 肿瘤坏死因子样凋亡微弱诱导剂；心肌成纤维细胞；P38丝裂原活化蛋白激酶；Ⅰ型胶原；基质金属蛋白酶1

Abstract:

Objective To investigate the mechanism and effects of tumor necrosis factor-like inducer of apoptosis (TWEAK) on expressions of collagen I and matrix metalloproteinase1(MMP-1) in cardiac fibroblasts(CFs). Methods Cultured CFs from neonatal Wistar rats were treated with the recombinant human TWEAK and the P38MAPK specific inhibitor(SB203580). CFs were divided into 3 groups: ① the control group: CFs were cultured without any stimulus; ② the TWEAK group: CFs were incubated with 100ng/mL TWEAK; ③ the TWEAK+SB203580 group: CFs were incubated with 100ng/mL TWEAK+SB203580. The CFs proliferation was examined by MTT, and expressions of collagen Ⅰ-and phosphor-P38MAPK protein were detected by Western blot. qRT-PCR was used to detect the collagen Ⅰ mRNA level. ELASA was used to detect the concentration of MMP1 in CFs cell-culture supernatant. Results TWEAK promoted the proliferation of the CFs and expressions of collagen Ⅰ and phosphor-P38MAPK protein. The expressions of collagen Ⅰ mRNA and MCP-1 were up regulated due to TWEAK. P38MAPK specific inhibitor (SB203580) could inhibit the proliferation of CFs. P38MAPK specific inhibitor (SB203580) could partially inhibit expressions of collagens Ⅰ mRNA , collagens Ⅰ protein, phosphor-P38MAPK protein and MMP-1. Conclusion TWEAK can promote expressions of collagen Ⅰ and MMP-1 in rat cardiac fibroblasts via P38MAPK pathway.

Key words: TWEAK; Cardiac fibroblasts; P38MAPK; Collagen I; MMP-1

中图分类号:

R542.2

王其磊1，任满意2，王德金1，徐冬玲1，杜贻萌1，王旭平3，隋树建1. TWEAK通过P38MAPK途径促进大鼠心肌成纤维细胞Ⅰ型胶原和MMP-1的表达[J]. 山东大学学报(医学版), 2012, 50(11): 43-47.

WANG Qi-lei1, REN Man-yi2, WANG De-jin1, XU Dong-ling1, DU Yi-meng1, WANG Xu-ping3, SUI Shu-jian1. TWEAK promotes expressions of collagen I and matrix metalloproteinase1
in rat cardiac fibroblasts via P38MAPK pathway[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2012, 50(11): 43-47.

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