Platelet-Derived Growth Factor Regulates the Biological Behavior of Oral Mucosal Fibroblasts by Inducing Cell Autophagy and Its Mechanism

Jie Wang; Lina Yang; Jialing You; Dada Wen; Bo Yang; Canhua Jiang

doi:10.2147/JIR.S313910

Platelet-Derived Growth Factor Regulates the Biological Behavior of Oral Mucosal Fibroblasts by Inducing Cell Autophagy and Its Mechanism

J Inflamm Res. 2021 Jul 17:14:3405-3417. doi: 10.2147/JIR.S313910. eCollection 2021.

Authors

Jie Wang^{1

2}, Lina Yang², Jialing You², Dada Wen², Bo Yang², Canhua Jiang¹

Affiliations

¹ Department of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South University, Changsha, 410078, People's Republic of China.
² Department of Immunology, Xiangya School of Medicine, Central South University, Changsha, 410078, People's Republic of China.

Abstract

Objective: To explore the effect of platelet-derived growth factor (PDGF) on oral mucosal fibroblast autophagy and further elucidate the molecular mechanism by which PDGF-BB regulates the biological behavior of oral mucosal fibroblasts by inducing autophagy.

Methods: Primary oral mucosal fibroblasts were isolated and cultured by the tissue block and trypsin methods and identified by indirect immunofluorescence vimentin detection. We detected the autophagy marker Beclin-1 and fibrosis marker Col-I of the primary oral mucosal fibroblasts at different time points after stimulating the fibroblasts with different PDGF-BB concentrations by Western blotting and determined the best experimental concentration and stimulation time of PDGF-BB. Then, indirect immunofluorescence, Western blotting, and quantitative real-time polymerase chain reaction (PCR) were used to detect the effect of PDGF-BB on the expression of autophagy-related and fibrotic proteins before and after 3-methyladenine (3-MA) intervention. Additionally, the effect of 3-MA on the proliferation and migration of primary oral mucosal fibroblasts stimulated by PDGF-BB was detected by the MTT method and a scratch experiment. The effect of PDGF-BB on Beclin-1 and phosphatidylinositol-3 kinase class 3 (PI3KC3) interaction was detected by co-immunoprecipitation.

Results: The results demonstrated that PDGF-BB could induce autophagy of the oral mucosal fibroblasts, showing a certain time and dose correlation. It induced cell autophagy through Beclin-1 and PI3KC3 interaction to promote the proliferation, migration, conversion, and collagen synthesis of the fibroblasts. However, 3-MA inhibited the combination of Beclin-1 and PI3KC3 and weakened the fibroblasts' proliferation, migration, conversion, and collagen synthesis activities.

Conclusion: Overall, PDGF-BB induces autophagy through the Beclin-1 pathway to regulate the biological behavior of oral mucosal fibroblasts.

Keywords: 3-MA; PDGF-BB; autophagy; biological behavior; primary oral mucosal fibroblasts; signaling pathway.

Grants and funding

National Natural Science Foundation of China, No.: 81271154. College Students’ Innovation Project of Central South University, S2020105330686. Changsha Municipal Natural Science Foundation: kq2014140.