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Urotensin II-induced collagen synthesis in cultured smooth muscle cells from rat aortic media and a possible involvement of transforming growth factor-beta 1/Smad2/3 signaling pathway
Zhao, Jing; Ding, Wenhui; Song, Nana; Dong, Xiao; Di, Beibing; Peng, Fen; Tang, Chaoshu
关键词Urotensin II Transforming growth factor-beta 1 Vascular smooth muscle cells Vascular fibrosis Vascular remodeling
刊名REGULATORY PEPTIDES
2013-03-10
DOI10.1016/j.regpep.2012.12.006
182页:53-58
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Endocrinology & Metabolism ; Physiology
研究领域[WOS]Endocrinology & Metabolism ; Physiology
关键词[WOS]NEONATAL CARDIAC FIBROBLASTS ; CONGESTIVE-HEART-FAILURE ; ADVENTITIAL FIBROBLASTS ; CAROTID ATHEROSCLEROSIS ; ENDOTHELIAL-CELLS ; RECEPTOR GPR14 ; ANGIOTENSIN-II ; PLASMA-LEVELS ; EXPRESSION ; HYPERTENSION
英文摘要

Background: Recent studies suggest that urotensin II (UII) and transforming growth factor-beta 1 (TGF-beta 1) both have critical roles in vascular remodeling. UII is a recently discovered vasoconstrictive peptide that is involved in the pathogenesis of atherosclerosis, restenosis and hypertension. TGF-beta 1 is an important factor that has a pivotal role in vascular fibrosis. This study aimed to explore whether TGF-beta 1 is involved in UII-induced collagen synthesis in rat aortic vascular smooth muscle cells (VSMCs) and examined the effects and mechanisms of UII on collagen synthesis and secretion in VSMCs.

Methods: VSMCs were prepared by the explant culture method. TGF-beta 1 and collagen I secretions from the cells were determined by enzyme-linked immunosorbent assay (ELISA). The mRNA and protein expressions of TGF-beta 1, collagen I, Smad2 and Smad3 were determined using Real-time RT-PCR and Western blotting.

Results: UII dose-dependently promoted TGF-beta 1 protein expression and secretion from VSMCs, with maximal effect at 10(-8) mol/l at 24 h for protein expression and 10(-7) mol/l at 24 h for protein secretion (both P<0.01). Moreover, UII dose-dependently promoted Smad2 and Smad3 mRNA expression in VSMCs, with maximal effect at 10-8 mol/l for 12 h (both P<0.01). The effects of UII were significantly inhibited by its receptor antagonists urantide (10(-6) mol/l) or SB-710411 (10-6 mol/l), and by the mitogen-activated protein kinase (MAPK/ERK) inhibitor PD98059 (10(-6) mol/l). UII dose-dependently promoted collagen I mRNA expression and protein secretion in VSMCs, with maximal effect at 10(-8) mol/l at 12 h for mRNA expression and 10-6 mo1/1 at 24 h for protein secretion (both P<0.01). Collagen synthesis and secretion from VSMCs induced by Ull were inhibited significantly by a TGF-beta 1-specific neutralizing antibody, SB-431542 (an antagonist of the TGF-beta 1 type II receptor) and PD98059 (all P<0.01).

Conclusions: This study suggests that Ull could induce collagen synthesis and secretion through upregulation of TGF-beta 1 expression and secretion in VSMCs, and that TGF-beta 1/Smad2/3 signaling might be one of the important pathways by which UII is involved in vascular fibrosis. (C) 2013 Elsevier B.V. All rights reserved.

语种英语
WOS记录号WOS:000317455200009
项目编号30871066 ; 81141003
资助机构National Natural Science Foundation of China
引用统计
被引频次:11[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/64633
专题北京大学第一临床医学院_心血管内科
作者单位Peking Univ, Dept Cardiol, Hosp 1, Beijing 100034, Peoples R China
推荐引用方式
GB/T 7714
Zhao, Jing,Ding, Wenhui,Song, Nana,et al. Urotensin II-induced collagen synthesis in cultured smooth muscle cells from rat aortic media and a possible involvement of transforming growth factor-beta 1/Smad2/3 signaling pathway[J]. REGULATORY PEPTIDES,2013,182:53-58.
APA Zhao, Jing.,Ding, Wenhui.,Song, Nana.,Dong, Xiao.,Di, Beibing.,...&Tang, Chaoshu.(2013).Urotensin II-induced collagen synthesis in cultured smooth muscle cells from rat aortic media and a possible involvement of transforming growth factor-beta 1/Smad2/3 signaling pathway.REGULATORY PEPTIDES,182,53-58.
MLA Zhao, Jing,et al."Urotensin II-induced collagen synthesis in cultured smooth muscle cells from rat aortic media and a possible involvement of transforming growth factor-beta 1/Smad2/3 signaling pathway".REGULATORY PEPTIDES 182(2013):53-58.
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