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Expression of smooth muscle cell‐specific proteins in neural progenitor cells induced by agonists of G protein‐coupled receptors and transforming growth factor‐β
Author(s) -
Morishita Rika,
Nagata Kohichi,
Ito Hidenori,
Ueda Hiroshi,
Asano Masahisa,
Shinohara Haruo,
Kato Kanefusa,
Asano Tomiko
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04405.x
Subject(s) - microbiology and biotechnology , rhoa , biology , transforming growth factor , progenitor cell , p19 cell , g protein coupled receptor , signal transduction , cellular differentiation , stem cell , biochemistry , adult stem cell , gene
Neural progenitor cells isolated from the embryonic cerebral cortex are well known to differentiate into neurons and glial cells, but recent reports have demonstrated differentiation into smooth muscle cells (SMCs) under the influence of fetal bovine serum. In this study, we report that agonists for G protein‐coupled receptors (GPCRs), including endothelin, lysophosphatidic acid and carbachol, effectively promote the expression of SMC‐specific proteins in the presence of transforming growth factor‐β (TGF‐β). Incubation of neural progenitor cells with agonists for GPCRs or TGF‐β alone induced the expression of an SMC‐specific protein, α‐smooth muscle actin (SMA), and their combination resulted in incremental increase. Stimulation with combinations of each GPCR agonist and TGF‐β increased the numbers of large, flat cells with thick actin fibers and also caused expression of other SMC marker proteins. Endothelin and TGF‐β enhanced SMA promoter‐luciferase reporter activity at different times after stimulation. The mutation of TGF‐β control element of SMA promoter constructs decreased TGF‐β‐enhanced luciferase activity but not endothelin‐stimulated activity. Transfection of active forms of RhoA and its effector, mDia, strongly enhanced SMA promoter activity, and a dominant negative form of RhoA inhibited endothelin‐stimulated promoter activity but not TGF‐β‐stimulated activity. Whereas endothelin consistently activated RhoA, TGF‐β did not, and a specific inhibitor of TGF‐β type I receptor blocked TGF‐β‐enhanced SMA promoter activity, suggesting involvement of Smad phosphorylation. These results suggest that separate signaling pathways of G protein and TGF‐β cooperatively promote the expression of SMC‐specific proteins in neural progenitor cells.