SMAD2 promotes myogenin expression and terminal myogenic differentiation

Abstract

SMAD2 is a transcription factor whose activity is regulated by members of the Transforming Growth Factor beta (TGFβ) superfamily. While activation of SMAD2 and SMAD3 downstream of TGFβ or myostatin signaling is known to inhibit myogenesis, we find that SMAD2 in the absence of TGFβ signaling promotes terminal myogenic differentiation. We find that during myogenic differentiation, SMAD2 expression is induced. Knockout of SMAD2 expression in primary myoblasts did not affect the efficiency of myogenic differentiation but produced smaller myotubes with reduced expression of the terminal differentiation marker myogenin. Conversely, overexpression of SMAD2 stimulated myogenin expression, and enhanced both differentiation and fusion, and these effects were independent of classical activation by the TGFβ receptor complex. Loss of Smad2 in muscle satellite cells in vivo resulted in decreased muscle fiber caliber and impaired regeneration after acute injury. Taken together, we demonstrate that SMAD2 is an important positive regulator of myogenic differentiation, in part through the regulation of Myog.

AMSTNDel273Cmutation withFGF5knockout sheep by CRISPR/Cas9 promotes skeletal muscle myofiber hyperplasia

“…Recently, a study on the downstream target gene Smad2 of MSTN showed that the knock-out of Smad2 expression in primary myoblasts did not affect the efficiency of myogenic differentiation, but produced smaller myotubes with reduced expression of the terminal differentiation marker myogenin. In turn, the overexpression of Smad2 stimulated the expression of myogenin and enhanced cell differentiation and fusion (Lamarche et al , 2021). In our study, the MSTN Del273C mutation with FGF5 knockout resulted in the inhibition of myogenic differentiation of skeletal muscle satellite cells, and the number of myotubes and the myotube size were significantly reduced.…”

Regulation of Myostatin on the Growth and Development of Skeletal Muscle

“…Notably, myostatin decreases the diameter of differentiated myotubes (Trendelenburg et al, 2009). Recently, a study on the downstream target of myostatin, Smad2, showed that the knock-out of Smad2 expression in primary myoblasts does not affect the efficiency of myogenic differentiation but produces smaller myotubes with reduced expression of the terminal differentiation marker, myogenin; conversely, overexpression of Smad2 stimulates the expression of myogenin and enhances cell differentiation and fusion (Lamarche et al, 2021).…”

Oat β‐glucan alleviates muscle atrophy via promoting myotube formation and suppressing protein degradation

“…After being stimulated by external harmful factors, the expression of myogenic regulatory factors (MRFs) such as Myf5, MRF4, myogenic differentiation antigen (MyoD), and myogenin (MyoG) is up‐regulated in satellite cells to activate myogenic differentiation and myotube formation for damaged muscles repair and regeneration 24,25 . Furthermore, MyoG protein level is also considered as an early marker of the myogenic differentiation process 26 . Beta‐myosin heavy chain (MyHC), an important functional motor protein, is the basic unit of thick filament of skeletal muscle fibers and generally regarded as a marker protein of the stage of myoblast differentiation 27,28 .…”

“…24,25 Furthermore, MyoG protein level is also considered as an early marker of the myogenic differentiation process. 26 Betamyosin heavy chain (MyHC), an important functional motor protein, is the basic unit of thick filament of skeletal muscle fibers and generally regarded as a marker protein of the stage of myoblast differentiation. 27,28 Myostatin (MSTN) is a class of growth regulator with the function of inhibiting muscle growth.…”