4.6 Article

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

Journal

JOURNAL OF INFLAMMATION RESEARCH
Volume 14, Issue -, Pages 3405-3417

Publisher

DOVE MEDICAL PRESS LTD
DOI: 10.2147/JIR.S313910

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Funding

  1. National Natural Science Foundation of China [81271154]
  2. College Students' Innovation Project of Central South University [S2020105330686]
  3. Changsha Municipal Natural Science Foundation [kq2014140]

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The study found that PDGF-BB can induce autophagy of oral mucosal fibroblasts through the interaction of Beclin-1 and PI3KC3, promoting cell proliferation, migration, and collagen synthesis. However, the inhibition of this interaction weakened the fibroblasts' activities. Overall, PDGF-BB regulates the biological behavior of oral mucosal fibroblasts by inducing autophagy through the Beclin-1 pathway.
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 coimmunoprecipitation. 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.

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