کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5823424 | 1118326 | 2014 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Endothelin-1 induces connective tissue growth factor expression in human lung fibroblasts by ETAR-dependent JNK/AP-1 pathway
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کلمات کلیدی
ECMα-SMAJnkCTGFETsBALGPCRET-1AP-1c-Jun N-terminal kinase - C-Jun N-terminal kinaseendothelin A receptor - اندوتلین گیرندهendothelin-1 - اندوتلین-1α-smooth muscle actin - اکتین عضله آلفا صافchromatin immunoprecipitation - ایمن سازی کروماتینBCE - بانک مرکزی اروپاDominant-negative mutant - جهش غالب منفیConnective tissue growth factor - فاکتور رشد بافت همبندbronchoalveolar lavage - لارو برونکلو آلوئولارExtracellular matrix - ماتریکس خارج سلولیactivator protein-1 - پروتئین فعال کننده-1CHiP - چیپG protein-coupled receptor - گیرندههای جفتشونده با پروتئین جی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
داروشناسی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Endothelin-1 induces connective tissue growth factor expression in human lung fibroblasts by ETAR-dependent JNK/AP-1 pathway Endothelin-1 induces connective tissue growth factor expression in human lung fibroblasts by ETAR-dependent JNK/AP-1 pathway](/preview/png/5823424.png)
چکیده انگلیسی
Endothelin-1 (ET-1) acts as a key mediator of vasoconstriction and tissue repair. Overproduction of connective tissue growth factor (CTGF) underlies the development of lung fibrosis. ET-1 induces expression of matrix-associated genes in lung fibroblasts, however, little is known about the signaling pathway of CTGF expression caused by ET-1. In this study, we found that ET-1 caused concentration- and time-dependently increases in CTGF expression in human embryonic lung fibroblast cell line (WI-38). ET-1-induced CTGF expression was inhibited by BQ123 (ETAR antagonist), but not BQ788 (ETBR antagonist). Moreover, ET-1-induced CTGF expression was significantly reduced by JNK inhibitor (SP600125), the dominant-negative mutants of JNK1/2 (JNK1/2 DN), and AP-1 inhibitor (curcumin). ET-1 induced phosphorylations of JNK and c-Jun in time-dependent manners. AP-1 luciferase activity was concentration-dependently increased by ET-1, and this effect was attenuated by SP600125. We also found that ET-1-induced CTGF expression was most controlled by the AP-1 binding region of CTGF promoter. ET-1-indiced CTGF luciferase activity was predominately controlled by the sequence â747 to â408 bp upstream of the transcription start site on the human CTGF promoter. Furthermore, ET-1 caused the formation of AP-1-specific DNA-protein complex and the recruitment of c-Jun to the CTGF promoter. Moreover, we found that ET-1 induced α-smooth muscle actin (α-SMA) expression, which was inhibited by BQ123, SP600125, curcumin, and anti-CTGF antibody. These results suggest that ET-1 stimulates expressions of CTGF and α-SMA through ETAR/JNK/AP-1 signaling pathway, and CTGF is required for ET-1-induced α-SMA expression in human lung fibroblasts.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 88, Issue 3, 1 April 2014, Pages 402-411
Journal: Biochemical Pharmacology - Volume 88, Issue 3, 1 April 2014, Pages 402-411
نویسندگان
Chih-Ming Weng, Chung-Chi Yu, Min-Liang Kuo, Bing-Chang Chen, Chien-Huang Lin,