Basic fibroblast growth factor is pro‐adipogenic in rat skeletal muscle progenitor clone, 2G11 cells

Abstract

Intramuscular adipose tissue (IMAT) formation is a hallmark of marbling in cattle. IMAT is considered to originate from skeletal muscle progenitor cells with adipogenic potential. However, the mechanism involved in IMAT formation from these progenitor cells in vivo remains unclear. In the present study, among the growth factors tested, which were known to be expressed in skeletal muscle, we found only basic fibroblast growth factor (bFGF) has a pro-adipogenic effect on skeletal muscle derived adipogenic progenitor clone, 2G11 cells. Pre-exposure of 2G11 cells to bFGF did not affect initial gene expressions of CCAAT/enhancer-binding protein (C/EBP)β and C/EBPδ, while resulting in an enhancement of subsequent expressions of C/EBPα and proliferator-activated receptor gamma (PPARγ) during adipogenesis, indicating that bFGF is acting on the transcriptional regulation of C/EBPα and PPARγ. In addition, the effect of bFGF is mediated via two types of FGF receptor (FGFR) isoforms: FGFR1 and FGFR2 IIIc, and both receptors are prerequisite for bFGF to express its pro-adipogenic effect. These results suggest that bFGF plays an important role as a key trigger of IMAT formation in vivo.

Oxidative stress-mediated senescence in mesenchymal progenitor cells causes the loss of their fibro/adipogenic potential and abrogates myoblast fusion

“…In sarcopenia, muscle frequently exhibits adipose- and fibrous-tissue infiltration [ 14 ], and this impairs skeletal muscle function: whereas intramuscular adipose tissue (IMAT) causes poor physical performance [ 15 ], fibrous tissue reduces motile and contractile functions [ 16 ]. Both IMAT and fibrous tissue have been widely shown to be derived from mesenchymal progenitor cells (MPCs), which reside in the interstitial space in skeletal muscle [ 17 , 18 ] and whose fibro/adipogenic potential is regulated by secreted growth factors: TGFβ upregulates the expression of the fibroblast markers collagen type 1 (Col1a1), connective-tissue growth factor (CTGF), and α-actin-2 (Acta2) [ 19 ], and basic fibroblast growth factor (bFGF) promotes the adipogenic programme of skeletal muscle adipogenic cells, as we reported previously [ 20 ]. Moreover, MPCs provide functional support to satellite cells and promote muscle regeneration [ 17 ].…”

“…To investigate whether senescence affects the adipogenic potential of 2G11 cells, PMS-2G11 cells were treated with bFGF, which exerts a pro-adipogenic effect on skeletal muscle adipogenic cells [ 20 ]. We immunocytochemically analysed Peroxisome proliferator-activated receptor (PPAR) γ and perilipin to assess adipogenicity ( Fig.…”

“…The primary antibodies used were anti-laminin (1:100, rabbit polyclonal; Sigma, St. Louis, MO, USA), anti-γH2AX (1:1000, rabbit polyclonal; Abcam, Cambridge, UK), anti-vimentin (1:100, rabbit polyclonal; Cell Signaling, Danvers, MA, USA) and anti-CSPG4 (1:50, mouse, clone 5C12, produced in our laboratory [ 20 ]).…”

“…Moreover, MPCs provide functional support to satellite cells and promote muscle regeneration [ 17 ]. We previously established the MPC clone 2G11 from rat skeletal muscle [ 21 ] and showed that 2G11 cells are fibro/adipogenic [ 20 , 22 ] and promote myotube formation by skeletal muscle progenitor cells [ 23 ]. Ageing causes a functional decrease in several cell types, but whether the fibro/adipogenic potential or the muscle-supportive effect of MPCs is perturbed in aged skeletal muscle remains to be elucidated.…”

Differentiation of skeletal muscle Mesenchymal progenitor cells to myofibroblasts is reversible

“…Thus, 2G11 cells are considered to be a useful MPC clone to elucidate the regulatory mechanism involved in fibrogenic/adipogenic differentiation of MPC. By using 2G11 cells as a model of MPC, we also reported that basic fibroblast growth factor (bFGF) has a pro‐adipogenic effect on MPC (Nakano et al, 2016). Therefore, it is possible that differentiation fate of MPC is regulated by the cross talk between TGF‐β and FGF signals.…”