Sparc, an EPS-induced gene, modulates the extracellular matrix and mitochondrial function via ILK/AMPK pathways in C2C12 cells.

Abstract

AIMS\nSecreted protein acidic and rich in cysteine, (SPARC), is a matricellular protein implicated in the modulation of the extracellular matrix (ECM) and mitochondrial proteins expression.\n\n\nMAIN METHODS\nTo study the mechanism through which SPARC is involved in the possible link between ECM and mitochondria, C2C12 myoblasts were cultured with/without the exogenous addition/inhibition of SPARC as well as activation/inhibition of adenosine monophosphate-activated protein kinase (AMPK). Electrical pulse stimulation (EPS), was applied for 2\u202fdays in myotubes.\n\n\nKEY FINDINGS\nThe expressions of ECM-related (integrin-linked kinase (ILK), glycogen synthase kinase-3 beta (GSK-3ß), phosphorylated-GSK-3ß (p-GSK-3ß) and collagen 1a1), mitochondrial-related (AMPK, phosphorylated-AMPK (p-AMPK), succinate dehydrogenase (SDHB) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc1α)) and SPARC proteins and/or genes were measured after modulation of SPARC and/or AMPK as well as with or without EPS. The addition of SPARC in C2C12 myoblast increased the expression of ILK, p-GSK-3ß and p-AMPK whereas anti-SPARC antibody decreased them at different incubation times (0, 10, and 30\u202fmin, and 6\u202fh). The AMPK activation increased SPARC, collagen 1a1, p-AMPK and SDHB proteins level, however, AMPK inhibition blunted the effects. EPS induced Sparc and Pgc1a genes expression.\n\n\nSIGNIFICANCE\nSparc, an EPS-induced gene, may be involved in the link between ECM remodeling and mitochondrial function in muscle via its interaction with ILK/AMPK.