Regulation of myogenic differentiation by type beta transforming growth factor.

Abstract

Abstract. Type 13 transforming growth factor (TGFI3) has been shown to be both a positive and negative regulator of cellular proliferation and differentiation. The effects of TGFI3 also are cell-type specific and appear to be modulated by other growth factors. In the present study, we examined the potential of TGFI3 for control of myogenic differentiation. In mouse C-2 myoblasts, TGFfl inhibited fusion and prevented expression of the muscle-specific gene products, creatine kinase and acetylcholine receptor. Differentiation of the nonfusing muscle cell line, BC3H1, was also inhibited by TGFI3 in a dose-dependent manner (IDs0 ~0.5 ng/ml). TGFI3 was not mitogenic for either muscle cell line, indicating that its inhibitory effects do not require cell proliferation. Inhibition of differentiation required the continual presence of TGFI3 in the culture media. Removal of TGFI3 led to rapid appearance of muscle proteins, which indicates that intracellular signals generated by TGFfl are highly transient and require continuous occupancy of the TGFI~ receptor. Northern blot hybridization analysis using a muscle creatine kinase cDNA probe indicated that TGFI3 inhibited differentiation at the level of muscle-specific mRNA accumulation. These results provide the first demonstration that TGFI3 is a potent regulator of myogenic differentiation and suggest that TGFI3 may play an important role in the control of tissue-specific gene expression during development.

Characterization of proliferating human skeletal muscle‐derived cells in vitro: Differential modulation of myoblast markers by TGF‐β2

“…TGF-b inhibits myoblast differentiation in some circumstances (Florini et al, 1986;Massague et al, 1986;Olson et al, 1986;Liu et al, 2001;Rousse et al, 2001) but stimulates it in others (Schofield and Wolpert, 1990;Zentella and Massague, 1992;De Angelis et al, 1998). We investigated whether TGF-b suppresses myoblast differentiation specifically in the context of adult HuSkMC proagated in mitogen-rich medium.…”

“…Myoblast differentiation is induced by reduction of serum and other mitogens in the culture medium (Allen et al, 1997), but some spontaneous differentiation will occur even in mitogen-rich cultures, especially at high cell density. Transforming growth factor b (TGF-b) has been reported by a number of investigators to suppress myoblast differentiation, primarily in studies performed on established cell lines under mitogen-poor conditions that inhibit myoblast proliferation (Florini et al, 1986;Massague et al, 1986;Olson et al, 1986;Liu et al, 2001;Rousse et al, 2001). Contradictory findings of TGF-b effects have been reported in the context of mitogen-rich medium used to culture the L6E9 myoblast cell line (Zentella and Massague, 1992), low cell density (De Angelis et al, 1998), and serum-free media (Schofield and Wolpert, 1990).…”

Oncogenic Ras-induced secretion of a novel inhibitor of skeletal myoblast differentiation

“…The inhibition of di erentiation by FGF-2, IGF-1, TGFb, or oncogenic Ras relies on continual signaling (Lathrop et al, 1985;Olson et al, 1986;Clegg et al, 1987;Gossett et al, 1988;Vaidya et al, 1989;Nakafuku et al, 1992). Induction of an autocrine loop would be an e cient mechanism to ensure a continual supply of inhibitor.…”

An inhibitor of transforming growth factor beta type I receptor ameliorates muscle atrophy in a mouse model of caveolin 3-deficient muscular dystrophy

“…Previous studies showed that myostatin, activin, or TGF-b1 impaired myogenic differentiation in cultured myogenic cells from several species. 27,[34][35][36] Using an efficient retroviral gene expression system, we confirmed that these three molecules independently suppressed mouse C2C12 myoblast differentiation. Conversely, the addition of Ki26894 almost completely restored the myotube formation that was impaired by the TGF-b family members.…”