PDGF-BB induces conversion, proliferation, migration, and collagen synthesis of oral mucosal fibroblasts through PDGFR-beta/PI3K/AKT signaling pathway

OBJECTIVE: To explore the pathogenesis of oral submucosal fibrosis (OSF) by analyzing the impact of Platelet Derived Growth Factor (PDGF)-BB on oral mucosal fibroblasts (FB) and PDGFR-beta/Phosphoinositide 3-kinase (PI3K)/serine/threonine protein kinase (AKT) signaling pathway. METHODS: The isolated and purified oral mucosal fibroblasts were divided into four groups: the control group (CON, 10% FBS DMEM), the PDGF-BB group (40 ng/ml PDGF-BB), the PDGF-BB+IMA group (40 ng/ml PDGF-BB and 60 mu mol/L IMA), and the PDGF-BB+LY294002 group (40 ng/ml PDGF-BB and 48 mu mol/L LY294002). Primary human FB cells were isolated and cultured for detecting the effects of PDGF-BB on alpha-smooth muscle actin (alpha-SMA) by indirect immunofluorescence. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, Thiazolyl Blue Tetrazolium Bromide (MTT) method and scratch test were used to detect the proliferation and migration of FB. Western blots were used to detect the synthesis of type I collagen (Col I) and the expression of PDGFR-beta/PI3K/AKT signaling pathway-related proteins. The effects of PDGFR-beta inhibitor and PI3K inhibitor were observed. RESULTS: Compared with group CON, group IMA, and group LY294002, alpha-SMA was upregulated in group PDGF-BB (p < 0.05), with higher OD490 nm value (p < 0.05), narrower average scratch width, and higher relative cell migration rate (p < 0.05). The expression levels of Col I, p-PDGFR-beta, p-PI3K, and p-AKT were higher in group PDGF-BB (p < 0.05). CONCLUSIONS: PDGF-BB induces FB to transform into myofibroblasts (MFB) through the PDGFR-beta/PI3K/AKT signaling pathway, and promotes the proliferation, migration, and collagen synthesis.

Automated summary

The study found that PDGF-BB induces oral mucosal fibroblasts to transform into myofibroblasts through the PDGFR-beta/PI3K/AKT signaling pathway, promoting proliferation, migration, and collagen synthesis.