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Notch and transforming growth factor‐beta signaling pathways cooperatively regulate vascular smooth muscle cell differentiation
Author(s) -
Tang Yuefeng,
Liaw Lucy
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.822.9
Subject(s) - notch signaling pathway , microbiology and biotechnology , vascular smooth muscle , smad , transforming growth factor , notch proteins , transforming growth factor beta , hes3 signaling axis , transcription factor , actin , biology , signal transduction , myosin , effector , chemistry , gene , endocrinology , genetics , smooth muscle
Notch and transforming growth factor‐beta (TGFβ) play pivotal roles during vascular development and the pathogenesis of vascular disease. The interaction of these two pathways is not fully understood. The present study utilized primary human smooth muscle cells (SMC) to examine molecular cross‐talk between TGFβ1 and Notch signaling on contractile gene expression. Activation of Notch signaling induced smooth muscle alpha‐actin (SM actin), smooth muscle myosin heavy chain (SM‐MHC), and calponin1, and the expression of Notch downstream effectors hairy‐related transcription factors (HRT). Similarly, TGFβ1 treatment of HASMC induced SM actin, calponin1, and smooth muscle protein 22‐α (SM22α) in a dose and time‐dependent manner. HRT proteins, which antagonize Notch activity, also suppressed the TGFβ1‐induced increase in SMC markers, suggesting a general mechanism of inhibition. We found that Notch and TGFβ1 cooperatively activate SMC marker transcripts and protein through parallel signaling axes. Moreover, the combination of Notch activation and TGFβ1 treatment led to synergistic activation of a TGFβ1 responsive SM specific gene promoter by the interaction of CBF1 and pSmad2/3. Thus, Notch and TGFβ1 coordinately induce a molecular and functional contractile phenotype by co‐regulation of Smad activity at SMC promoters. Grant Funding Source: NIH NCI