TGF-beta induces the differentiation of bone marrow stem cells into immature cardiomyocytes.
Transforming growth factor-beta(1) (TGF-beta(1)) was found to induce the myogenic differentiation of bone marrow stem cells (BMSC). We investigated the morphological and electrophysiological properties of differentiated cells, and the mechanisms related to TGF-beta(1)-induced myogenic differentiation. We found that TGF-beta increased the expression of the cardiac transcription factors, GATA-4 and NKx-2.5, in BMSC after 1-3 days of cultivation. TGF-beta also induced the expressions of cardiac myosin, troponins, and ANP after 3-14 days of cultivation. However, the Ca(2+) transient was relatively weak, the connexin-43 expression was irregular, and spontaneous beating was not detected within 28 days observation. TGF-beta stimulation up-regulated most of the TGF-beta BMP signaling pathway genes, including TGFBI, ACVR2B, and phosphorylated Smad-2 and Smad-3, within 24h. TGF-beta induced the differentiation of BMSC into immature cardiomyocytes by activating the TGF-beta BMP signaling pathway.
Li
Tao-Sheng
TS
Department of Surgery and Clinical Science, Yamaguchi University, Graduate School of Medicine, Minami-Kogushi 1-1-1, Ube, Yamaguchi 755-8505, Japan.
Komota
Takahiro
T
Ohshima
Mako
M
Qin
Shu-Lan
SL
Kubo
Masayuki
M
Ueda
Kazuhiro
K
Hamano
Kimikazu
K
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D024510:Muscle Development / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
D053773:Transforming Growth Factor beta1; D019009:Proto-Oncogene Proteins c-kit; D002118:Calcium