Premium
TGF‐beta downregulates Notch3 to promote differentiation of smooth muscle cells
Author(s) -
Lilly Brenda,
Kennard Simone
Publication year - 2007
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.21.5.a67-a
Subject(s) - microbiology and biotechnology , gene knockdown , cellular differentiation , vascular smooth muscle , myocyte , chemistry , smooth muscle , cell , transforming growth factor beta , intracellular , transforming growth factor , biology , gene , endocrinology , biochemistry
Vascular smooth muscle cells are an essential component of the blood vessel wall, yet the mechanisms that lead to their differentiation remain elusive. Notch family members have been implicated in blocking the differentiation of many cell types, and thus we sought to explore their role in smooth muscle differentiation. In contrast to Notch1, Notch3 is expressed in smooth muscle cells, and the smooth muscle precursors, 10T1/2 fibroblasts. Using TGF‐beta to induce the differentiation of 10T1/2 fibroblasts into smooth muscle cells, we investigated the specific function of Notch3. Knockdown of Notch3 by siRNA demonstrated that smooth muscle marker genes are repressed by Notch3, and consistent with this, overexpression of the Notch3 intracellular domain downregulated smooth muscle genes. Surprisingly, addition of TGF‐beta to 10T1/2 cells caused a significant decrease in Notch3 protein. Our data suggest that Notch3 serves to block smooth muscle differentiation, while TGF‐beta acts to overcome this blockade by altering its expression. These results offer a novel mechanism by which TGF‐beta promotes smooth muscle differentiation through the inhibition of Notch3.