TIEG1 negatively controls the myoblast pool indispensable for fusion during myogenic differentiation of C2C12 cells

Abstract

The transforming growth factor (TGF)-β inducible early gene (TIEG)-1 is implicated in the control of cell proliferation, differentiation, and apoptosis in some cell types. Since TIEG1 functioning may be associated with TGF-β, a suppressor of myogenesis, TIEG1 is also likely to be involved in myogenesis. Therefore, we investigated the function of TIEG1 during myogenic differentiation in vitro using the murine myoblasts cell line, C2C12. TIEG1 expression increased during differentiation of C2C12 cells. Constitutive expression of TIEG1 reduced survival and decreased myotube formation. Conversely, knocking down TIEG1 expression increased the number of viable cells during differentiation, and accelerated myoblast fusion into multinucleated myotubes. However, expression of the myogenic differentiation marker, myogenin, remained unaffected by TIEG1 knockdown. The mechanism underlying these events was investigated by focusing on the regulation of myoblast numbers after induction of differentiation. The knockdown of TIEG1 led to changes in cell cycle status and inhibition of apoptosis during the initial stages of differentiation. Microarray and real-time PCR analyses showed that the regulators of cell cycle progression were highly expressed in TIEG1 knockdown cells. Therefore, TIEG1 is a negative regulator of the myoblast pool that causes inhibition of myotube formation during myogenic differentiation.

Arsenic induces apoptosis in myoblasts through a reactive oxygen species-induced endoplasmic reticulum stress and mitochondrial dysfunction pathway

“…Once activated, satellite cells give rise to myoblasts that proliferate, differentiate, and fuse to form new muscle fibers or to repair damaged muscle fibers (Charge and Rudnicki 2004;Hawke and Garry 2001). A pool of myoblasts available for myogenesis is important for muscle size in vivo and in vitro (Miyake et al 2011). The decreased number of muscle fibers could be due to the decreased myoblast proliferation or cytotoxicity.…”

TIEG1 deficiency confers enhanced myocardial protection in the infarcted heart by mediating the Pten/Akt signalling pathway

“…TIEG1 expression is induced by TGF-β, bone morphogenetic proteins (BMPs) and other cytokines (7). It is located in multiple cell types and tissues, such as myocytes, tumour tissues and osteoblasts (8,9). The TIEG1 gene encodes a 72 kDa protein, which regulates cell growth and apoptosis (10,11).…”

“…However, the biological function of TIEG1 in the cardiovascular field remains unclear. In 2011, Miyake et al discovered that TIEG1 was a feedback regulator of myostatin in myoblasts (9), and Li et al illustrated that TIEG1 played a novel role as a blocker in angiotensin II (Ang II)-induced hypertrophy via the GATA binding protein 4 (GATA4) signalling pathway (15). …”

Thimerosal-Induced Apoptosis in Mouse C2C12 Myoblast Cells Occurs through Suppression of the PI3K/Akt/Survivin Pathway

“…Once activated, satellite cells give rise to myoblasts that proliferate, differentiate, and fuse to form new muscle fibers or repair damaged muscle fibers [23], [24]. Because a pool of myoblasts available for myogenesis is important for muscle size both in vivo and in vitro [25], decreased myoblast proliferation and cytotoxicity could lead to a decrease in the number of muscle fibers. Moreover, in most cases, apoptosis serves as a physiological mechanism to remove excess myoblasts during myogenesis or muscle regeneration, while inappropriate apoptosis could pathologically lead to degeneration such as that associated with various muscular dystrophies and atrophies [26]–[29].…”