Fibromodulin Modulates Chicken Skeletal Muscle Development via the Transforming Growth Factor-β Signaling Pathway

Abstract

Fibromodulin (Fmod), which is an extracellular matrix protein, belongs to the extracellular matrix small-leucine-rich proteoglycan family. Fmod is abundantly expressed in muscles and connective tissues and is involved in biological regulation processes, including cell apoptosis, cell adhesion, and modulation of cytokine activity. Fmod is the main regulator of myostatin, which controls the development of muscle cells, but its regulatory path is unknown. Chicken models are ideal for studying embryonic skeletal muscle development; therefore, to investigate the mechanism of Fmod in muscle development, Fmod-silenced and Fmod-overexpressed chicken myoblasts were constructed. The results showed that Fmod plays a positive role in differentiation by detecting the expression of myogenic differentiation markers, immunofluorescence of MyHC protein, and myotube formation in myoblasts. Fmod regulates expression of atrophy-related genes to alleviate muscle atrophy, which was confirmed by histological analysis of breast muscles in Fmod-modulated chicks in vivo. Additionally, genes differentially expressed between Fmod knockdown and normal myoblasts were enriched in the signaling pathway of transforming growth factor β (TGF-β). Both Fmod-silenced and Fmod-overexpressed myoblasts regulated the expression of TGFBR1 and p-Smad3. Thus, Fmod can promote differentiation but not proliferation of myoblasts by regulating the TGF-β signaling pathway, which may serve a function in muscular atrophy.

Vitamin C Promotes Muscle Development Mediated by the Interaction of CSRP3 with MyoD and MyoG

“…C2C12 cells were lysed with RIPA buffer . The lysate was centrifuged, and the supernatant was collected.…”

“…C2C12 cells were lysed with RIPA buffer. 27 The lysate was centrifuged, and the supernatant was collected. The anti-IgG (raised in rabbit, 1:50), anti-CSRP3 (raised in rabbit, 1:50), anti-MyoD (raised in rabbit, 1:50), and anti-MyoG (raised in rabbit, 1:50) antibodies were incubated with the protein A/G magnetic beads at 4 °C for 2 h. Next, the supernatant was incubated with the antibodymagnetic bead complexes at 4 °C for 2 h. The magnetic beads were separated and incubated with 1× SDS-PAGE loading buffer at 95 °C for 5 min.…”

Defect in cytosolic Neu2 sialidase abrogates lipid metabolism and impairs muscle function in vivo

“…Among the sialylated glycoproteins identified, the fibromodulin (Fmod) protein is a main regulator of myostatin, which controls the development of muscle cells, and is abundantly expressed in muscles and connective tissues. The Fmod protein regulates the expression of atrophy-related genes to alleviate muscle atrophy by regulating the TGF signaling pathway 25 , 26 . In contrast, myogenesis regulating glycosidase (MYORG) is a glycosidase that has an important role in myoblast differentiation and is involved in movement disorders and cognitive impairment 27 , 28 .…”

Identification of the differentially expressed genes in the leg muscles of Zhedong white geese (Anser cygnoides) reared under different photoperiods

“…Among these DEGs, FMOD, HSPB1, and STC1 were upregulated in the goose leg muscles under SL condtions. FMOD promotes chicken myogenic cell differentiation and alleviates muscle atrophy ( Yin et al, 2020 ). Inhibition of HSPB1 during myogenesis represses myotube formation ( Kim et al, 2018 ).…”