Dermatopontin in Skeletal Muscle Extracellular Matrix Regulates Myogenesis

Abstract

Dermatopontin (DPT) is an extensively distributed non-collagenous component of the extracellular matrix predominantly found in the dermis of the skin, and consequently expressed in several tissues. In this study, we explored the role of DPT in myogenesis and perceived that it enhances the cell adhesion, reduces the cell proliferation and promotes the myoblast differentiation in C2C12 cells. Our results reveal an inhibitory effect with fibronectin (FN) in myoblast differentiation. We also observed that DPT and fibromodulin (FMOD) regulate positively to each other and promote myogenic differentiation. We further predicted the 3D structure of DPT, which is as yet unknown, and validated it using state-of-the-art in silico tools. Furthermore, we explored the in-silico protein-protein interaction between DPT-FMOD, DPT-FN, and FMOD-FN, and perceived that the interaction between FMOD-FN is more robust than DPT-FMOD and DPT-FN. Taken together, our findings have determined the role of DPT at different stages of the myogenic process.

Cross-Talk Between Extracellular Matrix and Skeletal Muscle: Implications for Myopathies

“…Cell-matrix communication contribute a vital role in cell adhesion and migration, and therefore, is critically important during embryonic and adult myogenesis (Goody et al, 2015). Various ECM proteins (e.g., dermatopontin, nidogen/entactin, periostin, and osteopontin) contribute to the regulations of cellmatrix communications and matrix assembly (Funanage et al, 1992;Norris et al, 2007;Kato et al, 2011;Kim et al, 2019).…”

“…Skeletal muscle (SM) is a contractile tissue primarily comprised of multinucleated myofibers. SM is one of the most important plastic tissues in the human body and accounts for around 40% of total body weight (Campbell and Stull, 2003;Frontera and Ochala, 2015;Kim et al, 2019). SMs contain multipotent precursor cells called muscle satellite cells (MSCs), which are localized below the basal lamina (BL) in myofibers, play vital roles in maintaining the integrity of SM, and participate in muscles regeneration via an organized myogenic program (Asakura et al, 2001).…”

“…The developmental process of multinucleated myofibers with contractile capability from MSCs is termed myogenesis, and involves cell cycle arrest, cell fusion, increases in nuclear sizes, and the peripheral localization of nuclei (Charge and Rudnicki, 2004). Myogenesis is a decidedly regulated mechanism that is determined by the co-expressions of Pax3, Pax7, and myogenicregulatory factors such as Myf5, Mrf4, MyoD, and myogenin in MSCs (Zammit and Beauchamp, 2001;Relaix et al, 2005;Baig et al, 2019;Kim et al, 2019;Lee et al, 2019).…”

“…Furthermore, two major SM ECM proteins, that is, collagen and laminin, are known to be associated with myopathies. In previous studies, we explored the roles of a small number of ECM proteins like fibromodulin, matrix gla proteins, and dermatopontin during different stages of myogenesis (Lee et al, 2016;Ahmad et al, 2017;Lee et al, 2018;Kim et al, 2019) and found fibromodulin, as well as dermatopontin, is involved in the vigorous recruitment of MSCs at sites of injury, and thus, aids SM regeneration Kim et al, 2019).…”

Dermatopontin, A Novel Adipokine Promoting Adipose Tissue Extracellular Matrix Remodelling and Inflammation in Obesity

“…Reportedly, DPT is a potent cell adhesion molecule in diverse cell types including keratinocytes, fibroblasts and endothelial cells [17,18]. DPT has also been involved in inhibiting cell proliferation such as in murine C2C12 myoblasts, keratinocytes, osteosarcoma MG-63 cells or papillary thyroid cancer cells [4,19]. Moreover, DPT has been found in wound fluids as well as in the provisional matrix, a term to describe factors that appear coincident with epidermal cell migration during skin wound healing [4].…”