Cx43 contributes to TGF-beta signaling to regulate differentiation of cardiac fibroblasts into myofibroblasts.
Differentiation and activation of fibroblasts into myofibroblasts which express alpha-smooth muscle actin (alpha-SMA) are essential for wound healing and tissue repair. Change in fibroblast properties is initiated by transforming growth factor beta (TGF-beta). Here, we sought to investigate whether connexin43 (Cx43), a gap-junctional protein, contributes to differentiation of cardiac fibroblasts to myofibroblasts. In cultured neonatal rat cardiac fibroblasts, we found that expression of alpha-SMA increases in parallel with Cx43 by using immunocytochemistry, and that knockdown of the endogenous Cx43 activity with antisense oligodeoxynucleotides (AS) inhibits alpha-SMA expression significantly, while overexpression of Cx43 increases alpha-SMA expression remarkably. These findings demonstrate that Cx43 contributes to TGF-beta signaling to regulate alpha-SMA expression. Thus, we propose a novel physiologic function of Cx43, which plays a critical role in the pathological activation of cardiac fibroblasts in the myocardial fibrosis associated with heart failure.
Asazuma-Nakamura
Yuko
Y
Department of Pathology and Cell Regulation, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan.
Dai
Ping
P
Harada
Yoshinori
Y
Jiang
Yan
Y
Hamaoka
Kenji
K
Takamatsu
Tetsuro
T
D000199:Actins / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000502:physiology*; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D006333:Heart Failure; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D018031:Connexin 43; D016212:Transforming Growth Factor beta; C498862:Acta2 protein, rat