Mechanism of adipose tissue-derived stromal cell-extracellular vesicles in treating oral submucous fibrosis by blocking the TGF-β1/Smad3 pathway via the miR-760-3p/IGF1R axis

Authors

  • Fengcong Wang Department of Orthodontics, Jinan Stomatological Hospital, Shandong, China
  • Li Jiang Department of Endodontics, Jinan Stomatological Hospital, Shandong, China
  • Ping Liu Department of Orthodontics, Jinan Stomatological Hospital, Shandong, China
  • Yanjun Jiang Engineering Laboratory for Biomaterials and Tissue Regeneration, Ningbo Stomatology Hospital, Zhejiang, China

DOI:

https://doi.org/10.17305/bb.2023.9944

Keywords:

Adipose tissue-derived stromal cells (ADSCs), extracellular vesicles (EVs), fibrotic buccal mucosal fibroblasts (fBMFs), insulin-like growth factor 1 receptor (IGF1R), miR-760-3p, oral submucous fibrosis (OSF), TGF-β1/Smad3

Abstract

Oral submucous fibrosis (OSF) is a prevalent chronic condition, and understanding its pathogenesis is crucial for developing effective therapeutic strategies. This study explores the potential of adipose tissue-derived stromal cell-extracellular vesicles (ADSC-EVs) in mitigating OSF and investigates the underlying molecular mechanisms. OSF was induced in mice by arecoline feeding. Adipose tissue-derived stromal cells (ADSCs), fibrotic buccal mucosal fibroblasts (fBMFs) isolated from OSF mice, and ADSC-EVs were comprehensively characterized. The treatment effects of extracellular vesicles (EVs) and pcDNA3.1-IGF1R on fBMF proliferation, migration, and invasion were assessed using Cell Counting Kit-8 (CCK-8) assay, transwell assay, and flow cytometry assay. The expression levels of alpha-smooth muscle actin (α-SMA), collagen I, collagen III, and insulin-like growth factor 1 receptor (IGF1R) were evaluated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot. The interaction between miR-760-3p and IGF1R was investigated. In fBMFs and OSF mice treated with a miR-760-3p inhibitor and/or EVs, the expression patterns of miR-760-3p, IGF1R, and proteins related to the TGF-β1/Smad3 pathway were determined. ADSC-EVs demonstrated the ability to upregulate miR-760-3p, impede cell proliferation, migration, and invasion, and reduce α-SMA, collagen I, and collagen III levels in fBMFs. The expression of miR-760-3p was diminished in ADSC-EVs treated with a miR-760-3p inhibitor. However, silencing miR-760-3p or overexpressing IGF1R partially counteracted the beneficial effects of ADSC-EVs on fBMF fibrosis. miR-760-3p directly targets IGF1R. Significantly, ADSC-EVs exert their suppressive effects on the TGF-β1/Smad3 pathway through the miR-760-3p/IGF1R axis. In summary, ADSC-EVs, by transferring miR-760-3p and inhibiting IGF1R expression, effectively block the TGF-β1/Smad3 pathway, thereby alleviating fibrosis in fBMFs and preventing the progression of OSF.

Adipose tissue-derived stromal cell-extracellular vesicles ameliorate oral submucous fibrosis by blocking the TGF-β1/Smad3 pathway via the miR-760-3p/IGF1R axis

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Published

04-12-2023

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Section

Molecular Biology

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How to Cite

1.
Mechanism of adipose tissue-derived stromal cell-extracellular vesicles in treating oral submucous fibrosis by blocking the TGF-β1/Smad3 pathway via the miR-760-3p/IGF1R axis. Biomol Biomed [Internet]. 2023 Dec. 4 [cited 2024 Mar. 3];. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/9944