期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
卷 1867, 期 12, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.bbamcr.2020.118848
关键词
G protein-coupled receptor; Kinase receptors; Smads; Vascular smooth muscle cells; Biglycan; TGF-beta receptor
资金
- National Health and Medical Research Council of Australia [1022800]
- National Heart Foundation of Australia [G09M4385, 102129, 102761]
- Diabetes Australia Research Trust
- Academic support packages the University of Queensland
- Research Training Scholarship of The University of Queensland
- NHMRC-Peter Doherty [1160925]
- National Health and Medical Research Council of Australia [1160925] Funding Source: NHMRC
Lysophosphatidic acid (LPA) via transactivation dependent signalling pathways contributes to a plethora of physiological and pathophysiological responses. In the vasculature, hyperelongation of glycosaminoglycan (GAG) chains on proteoglycans leads to lipid retention in the intima resulting in the early pathogenesis of atherosclerosis. Therefore, we investigated and defined the contribution of transactivation dependent signalling in LPA mediated GAG chain hyperelongation in human vascular smooth muscle cells (VSMCs). LPA acting via the LPA receptor 5 (LPAR5) transactivates the TGFBR1 to stimulate the mRNA expression of GAG initiation and elongation genes xylosyltransferase-1 (XYLT1) and chondroitin 6-sulfotransferase-1 (CHST3), respectively. We found that LPA stimulates ROS and Akt signalling in VSMCs, however they are not associated in LPAR5 transactivation of the TGFBR1. We observed that LPA via ROCK dependent pathways transactivates the TGFBR1 to stimulate genes associated with GAG chain elongation. We demonstrate that GPCR transactivation of the TGFBR1 occurs via a universal biochemical mechanism and the identified effectors represent potential therapeutic targets to inhibit pathophysiological effects of GPCR transactivation of the TGFBR1.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据