Fibroblast growth factor-2 stimulates proliferation of human adipose-derived stem cells via Src activation

Abstract

BackgroundHuman adipose-derived stem cells (hASCs) are a subset of mesenchymal stem cells (MSCs); it has been regarded as one of the most promising stem cells. We previously found that fibroblast growth factor-2 (FGF-2) enhanced the proliferation and differentiation of hASC. However, the mechanisms involved in the growth of hASCs by FGF-2 have not been investigated.MethodsHuman adipose-derived stem cells (hASCs) were cultured with FGF-2, and cell growth was assessed. Effects of FGF Receptor (FGFR) inhibitor (NVP-BGJ398), ERK1/2 inhibitor (PD98059), PI3K/Akt inhibitor (LY294002), JNK inhibitor (SP600125), and p38 MAPK inhibitor (SB203580) and Src inhibitor (PP1) on the proliferation were investigated. At the same time, we assessed the effect of FGFR inhibitor on several signaling enzymes such as ERK1/2, JNK, p38, and Akt, in protein level. The involvement of Src activation by FGF-2 was also examined.ResultsFGF-2 markedly promoted proliferation of hASCs at concentrations lower than 10 ng/ml and stimulated cell progression to the S and G2/M phases. Proliferation was blocked by the FGFR inhibitor (NVP-BGJ398) and various signaling pathway inhibitors, such as Erk1/2 inhibitor (PD98059), PI3K/Akt inhibitor (LY294002), JNK inhibitor (SP600125), and p38MAPK inhibitor (SB203580). The FGFR inhibitor reduced the activation of protein kinases, such as AKT, Erk1/2, JNK, and p38, in several signaling pathways. The downstream kinase of FGFR, Src, was activated by FGF-2, and its activation was canceled by the FGFR inhibitor. MEK1/2, a downstream kinase of Src, was parallelly regulated by FGF-2. The Src inhibitor (PP1) markedly blocked the proliferation of hASCs via inhibition of Src and MEK1/2.ConclusionSrc activation is indispensable for FGF-2-mediated proliferation of ASCs, as well as the subsequent activation of multi-signaling pathways.

Effects and mechanisms of basic fibroblast growth factor on the proliferation and regenerative profiles of cryopreserved dental pulp stem cells

“…bFGF participates in proliferation and self‐renewal of stem cells 38,39 . Previous study demonstrated that 5 ng/mL bFGF effectively enhanced the proliferation of bone marrow mesenchymal stem cells 31 .…”

“…bFGF participates in proliferation and self-renewal of stem cells. 38,39 Previous study demonstrated that 5 ng/mL bFGF effectively enhanced the proliferation of bone marrow mesenchymal stem cells. 31 And we discovered that 20 ng/mL bFGF significantly boosted up the viability of post-thawed DPSCs, and this advantageous effect emerged at day 5 ( Figure 1C).…”

Fibroblast growth factor 2 suppresses the expression of C-C motif chemokine 11 through the c-Jun N-terminal kinase pathway in human dental pulp-derived mesenchymal stem cells

“…In addition, FGFR is a family of tyrosine kinases that can activate signaling cascades, such as RAS-MAPK, PI3K-AKT, phospholipase C γ and STAT (48). Among the downstream mediators of FGF2 signaling pathways, the MAPK pathway has been demonstrated to play a pivotal role in the function of stem cells, including mesenchymal stem cells (49)(50)(51). Thus, the present study focused on the MAPK pathway and found that FGF2 induced the phosphorylation of p38 MAPK, ERK1/2 and JNK in SDP11 cells.…”

Changing Expression Profiles and Inclination to Competing Endogenous RNA Networks on MAPK Signaling Pathways of Human Adipose-Derived Stem Cells in a Direct Current Electric Field

“…Upregulated and downregulated mRNAs were enriched to GO terms and KEGG pathways. Among all the related pathways, the MAPK signaling pathway, which is also an important pathway regulating ADSC proliferation [ 38 ], differentiation [ 39 ], and migration [ 40 ], had the highest gene ratio in the upregulated mRNA enriched pathways. To screen the three terms related to MAPK signaling pathway, all the BP terms enriched by differential expressed mRNAs were calculated ( p < 0.05).…”