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Transforming Growth Factor‐β stimulates smooth muscle differentiation in epicardial cells lacking the Type III Receptor
Author(s) -
Barnett Joey V.,
Compton Leigh A.,
Love Joey D.,
Austin Anita F.
Publication year - 2008
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.22.1_supplement.590.2
Subject(s) - transforming growth factor , null cell , biology , receptor , microbiology and biotechnology , endocrinology , medicine , wild type , embryonic stem cell , myocyte , cell type , cell , cell culture , gene , mutant , genetics
Transforming growth factor (TGF) β receptor III (TGFβR3) binds all 3 TGFβ ligands and inhibin with high affinity but lacks the serine/threonine kinase domain found in the type I and type II receptors (TGFβR1, TGFβR2). TGFβR3 facilitates signaling via TGFβR1/TGFβR2 but also has been suggested to play a unique and nonredundant role in TGFβ signaling. Coronary vessel development is impaired in Tgfbr3 null mice with few vessels formed and mice die at embryonic day (E) 14.5. In null mice, vessels throughout the yolk sac and embryo form and recruit smooth muscle in a pattern indistinguishable from heterozygous or wild‐type littermates. Null mice form 2 coronary ostia and appear to initiate smooth muscle recruitment by E14. To directly address the role of Tgfbr3 in smooth muscle differentiation in epicardial cells we generated immortalized cell lines from wildtype, heterozygous null, and null animals at E11.5 and E13.5. Cells from all genotypes grew as tightly packed epithelium and expressed Zonula Occludens‐1 (ZO‐1). The addition of 250 pM TGFβ1 or TGFβ2 demonstrated a loss of epithelial morphology as measured by the loss of ZO‐1. TGFβ1 or TGFβ2 induced the smooth muscle marker SM22α in all genotypes. Therefore, TGFβR3 is not required in epicardial cells for smooth muscle differentiation and the defect in coronary vessel development seen in Tgfbr3 null mice is likely not due to defects in smooth muscle recruitment.