TY - JOUR
T1 - Production of activin A and follistatin in cultured rat vascular smooth muscle cells
AU - Kanzaki, Makoto
AU - Nobusawa, Romi
AU - Mogami, Hideo
AU - Yasuda, Hiroshi
AU - Kawamura, Norio
AU - Kojima, Itaru
PY - 1995/2/27
Y1 - 1995/2/27
N2 - Activin A, a member of the transforming growth factor β supergene family, modulates DNA synthesis in cultured rat vascular smooth muscle cells (VSMC) (Kopma et al. (1993) Exp. Cell. Res. 206, 152-156). In the present study, we studied the production of activin A and follistatin in VSMC. When VSMCs cultured in a 24-well plate were cultured with 10% fetal calf serum (FCS) for 24 h, 0.94 ± 0.20 pmol/well (mean ± SE, n = 6) of bioactive activin was released into the culture media. Reverse-transcription polymerase chain-reaction revealed the expression of mRNA for the βA subunit of inhibin but not for either the βB or α subunit. Bioactivity of activin was increased in quiescent cells treated with FCS or platelet-derived growth factor (PDGF) but not with angiotensin II (Ang II) or insulin-like growth factor-I (IGF-I). Ang II or IGF-I did not stimulate DNA synthesis by itself but, when these two agents were combined, they increased nuclear labeling by 16.4% and release of bioactive activin by 170% of basal. The dose-response relationship and time course study indicated that PDGF-mediated release of activin correlated with initiation of DNA synthesis. Steady state expression of mRNA for the βA subunit was markedly elevated 12 h after the addition of PDGF and was reduced thereafter. To assess the significance of autocrine activin, the effect of PDGF was determined in the presence and absence of excess of exogenous follistatin. The PDGF-mediated DNA synthesis was enhanced by the addition of excess follistatin. In addition to the production of activin, PDGF also enhanced release of follistatin from VSMC. These results indicate that VSMC synthesize and release both activin and follistatin and that the activin-follistatin system may modulate DNA synthesis in VSMC.
AB - Activin A, a member of the transforming growth factor β supergene family, modulates DNA synthesis in cultured rat vascular smooth muscle cells (VSMC) (Kopma et al. (1993) Exp. Cell. Res. 206, 152-156). In the present study, we studied the production of activin A and follistatin in VSMC. When VSMCs cultured in a 24-well plate were cultured with 10% fetal calf serum (FCS) for 24 h, 0.94 ± 0.20 pmol/well (mean ± SE, n = 6) of bioactive activin was released into the culture media. Reverse-transcription polymerase chain-reaction revealed the expression of mRNA for the βA subunit of inhibin but not for either the βB or α subunit. Bioactivity of activin was increased in quiescent cells treated with FCS or platelet-derived growth factor (PDGF) but not with angiotensin II (Ang II) or insulin-like growth factor-I (IGF-I). Ang II or IGF-I did not stimulate DNA synthesis by itself but, when these two agents were combined, they increased nuclear labeling by 16.4% and release of bioactive activin by 170% of basal. The dose-response relationship and time course study indicated that PDGF-mediated release of activin correlated with initiation of DNA synthesis. Steady state expression of mRNA for the βA subunit was markedly elevated 12 h after the addition of PDGF and was reduced thereafter. To assess the significance of autocrine activin, the effect of PDGF was determined in the presence and absence of excess of exogenous follistatin. The PDGF-mediated DNA synthesis was enhanced by the addition of excess follistatin. In addition to the production of activin, PDGF also enhanced release of follistatin from VSMC. These results indicate that VSMC synthesize and release both activin and follistatin and that the activin-follistatin system may modulate DNA synthesis in VSMC.
KW - Activin A
KW - Follistatin
KW - Vascular smooth muscle cell
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U2 - 10.1016/0303-7207(94)03451-X
DO - 10.1016/0303-7207(94)03451-X
M3 - Article
C2 - 7758823
AN - SCOPUS:0028957524
VL - 108
SP - 11
EP - 16
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
SN - 0303-7207
IS - 1-2
ER -