Adipose-derived mesenchymal stem cell exosomes inhibit transforming growth factor-[beta]1-induced collagen synthesis in oral mucosal fibroblasts

• Published in: Experimental and therapeutic medicine Vol. 22; no. 6
• Main Authors: Liu, Junjie, Li, Fuxingzi, Liu, Binjie, Yao, Zhigang, Li, Long, Liu, Gui, Peng, Lei, Wang, Yuxin, Huang, Junhui
• Format: Journal Article
• Language: English
• Published: Spandidos Publications 01.12.2021
• Subjects: Care and treatment; Cell organelles; Collagen; Development and progression; Fibrosis; Health aspects; Mouth diseases; Physiological aspects; Stem cells; Transforming growth factors; China
• ISSN: 1792-0981
• DOI: 10.3892/etm.2021.10854

Oral submucosal fibrosis (OSF) is a potentially malignant oral disorder that requires the further development of advanced treatment strategies. TGF-[beta]1 has been reported to be the main trigger for the increased collagen production and reduced activity of matrix degradation pathways in OSF. Exosomes are key mediators of paracrine signaling that have been proposed for direct use as therapeutic agents for tissue repair and regeneration. The present study aimed to investigate the effects of human adipose-derived mesenchymal stem cell (ADSC) exosomes (ADSC-Exos) on TGF-[beta]1-treated oral fibroblasts in vitro and to unravel the potential underlying mechanism of action. Oral mucosal fibroblasts were obtained from the buccal tissues of patients without OSF during extraction of the third molar. ADSCs were obtained from three healthy female individuals during liposuction procedures. ADSC-Exos were isolated by ultracentrifugation and identified by electron microscopy, nanoparticle tracking and western blotting. Immunofluorescence and immunocytochemistry staining were performed to measure the expression levels of vimentin and [alpha]-smooth muscle actin in the fibroblasts. Reverse transcription-quantitative PCR and western blotting were used to determine the expression levels of mRNAs and proteins associated with collagen production. The p38 MAPK activator anisomycin was used to identify the underlying mechanisms of the effects of ADSC-Exos on TGF-[beta]1-induced collagen synthesis in oral mucosal fibroblasts. The results of the present study revealed that ADSC-Exos exhibited a cup- or sphere-shaped morphology, with a mean diameter of 58.01 [+ or -] 16.17 nm. ADSC-Exos were also found to be positive for CD63 and tumor susceptibility 101 expression. ADSC-Exos treatment reversed the TGF-[beta]1-induced upregulation of collagen I and III protein expression. In addition, in the presence of TGF-[beta]1, the expression levels of collagen type I a 1 chain and collagen type III a 1 chain mRNA were downregulated, whilst the expression levels of matrix metalloproteinase (MMP)1 and MMP3 were upregulated following ADSC-Exos treatment. The TGF-[beta]1-induced upregulation in the phosphorylation of p38 in addition to the increased protein expression of collagens I and III were also reversed in fibroblasts following ADSC-Exos treatment. However, anisomycin treatment alleviated these ADSC-Exos-induced changes. In conclusion, findings from the present study suggest that ADSC-Exos may represent a promising strategy for OSF treatment by targeting the p38 MAPK signaling pathway. Key words: adipose-derived mesenchymal stem cell exosomes, fibroblasts, TGF-[beta]1, collagen synthesis, oral submucous fibrosis