Lactoferrin promotes murine C2C12 myoblast proliferation and differentiation and myotube hypertrophy

Abstract

Lactoferrin (Lf) is a multifunctional glycoprotein, which promotes the proliferation of murine C2C12 myoblasts. In the present study, it was investigated how Lf promotes myoblast proliferation and whether Lf promotes myoblast differentiation or induces myotube hypertrophy. Lf promoted the proliferation of myoblasts in a dose-dependent manner. Myoblast proliferation increased on day 3 when myoblasts were cultured in the presence of Lf for three days and also when myoblasts were cultured in the presence of Lf for the first day and in the absence of Lf for the subsequent two days. In addition, Lf induced the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 in myoblasts. The mitogen-activated protein kinase kinase 1/2 inhibitor U0126 inhibited Lf-induced ERK1/2 phosphorylation and repressed Lf-promoted myoblast proliferation. C2C12 myoblasts, myotubes and skeletal muscle expressed low-density lipoprotein receptor-related protein (LRP)1 mRNA and Lf-promoted myoblast proliferation was attenuated by an LRP1 antagonist or LRP1 gene silencing. The knockdown of LRP1 repressed Lf-induced phosphorylation of ERK1/2. Furthermore, when myoblasts were induced to differentiate, Lf increased the expression of the myotube-specific structural protein, myosin heavy chain (MyHC) and promoted myotube formation. Knockdown of LRP1 repressed Lf-induced MyHC expression. Lf also increased myotube size following differentiation. These results indicate that Lf promotes myoblast proliferation and differentiation, at least partially through LRP1 and also stimulates myotube hypertrophy.

Lactoferrin Deficiency Impairs Proliferation of Satellite Cells via Downregulating the ERK1/2 Signaling Pathway

“…Many studies confirmed that the ERK1/2 signaling pathway plays an important role in regulating the proliferation of SCs and myoblasts [26,27,46]. Additionally, Ltf partially affects C2C12 cell proliferation and differentiation through the Lrp1 receptor-mediated ERK1/2 signaling pathway [7]. Studies have reported that Ltf plays an important role in bone [47], hair [9] and skin regeneration [40], which is mainly achieved by mediating the ERK signaling pathway.…”

“…To verify the effect of Ltf on the proliferation ability of SCs, we treated the SCs with various concentrations of exogenous R-Ltf. It has been reported that exogenous Ltf promotes the proliferation of C2C12 cells and myogenic differentiation, thereby promoting myotube hypertrophy [7]. Zhang et al [50] showed that Ltf promoted human tenocyte proliferation and collagen synthesis at a concentration of 100 µg/mL.…”

“…Recent studies have focused on Ltf as a biologically active factor that regulates cell proliferation and differentiation. Kitakaze et al [7] found that Ltf led to increased cell proliferation when C2C12 is exposed to Ltf for only the first day. Additionally, Ltf promotes C2C12 differentiation and myotube hypertrophy through the low-density lipoprotein receptor mediated ERK1/2 signaling pathway.…”

Colostrum-Induced Temporary Changes in the Expression of Proteins Regulating the Epithelial Barrier Function in the Intestine

“…Several studies indicate that Lf can induce the expression of the myosin heavy chain and promote myotube formation in myoblasts [ 38 ]. Since the cytoskeleton is a key element in assembling intercellular junctions, we considered it necessary to evaluate the expression level of MYH9 and ACTG2 in response to Col treatment.…”

Beta-agonist drugs modulate the proliferation and differentiation of skeletal muscle cells in vitro

“…Images of six different and random spots were captured per coverslip on Nikon eclipse TS 100 microscope. For calculation, the fusion index was evaluated as the ratio of the number of nuclei within myotubes containing two or more nuclei to the total number of nuclei for the six fields [ 23 ].…”