Exosomes derived from bone marrow mesenchymal stem cells reverse epithelial-mesenchymal transition potentially via attenuating Wnt/β-catenin signaling to alleviate silica-induced pulmonary fibrosis

Abstract

Pulmonary fibrosis induced by silica dust is an irreversible, chronic, and fibroproliferative lung disease with no effective treatment at present. BMSCs-derived exosomes (BMSCs-Exo) possess similar functions to their parent cells. In this study, we investigated the therapeutic potential and underlying molecular mechanism for BMSCs-Exo in the treatment of silica-induced pulmonary fibrosis. The rat model of experimental silicosis pulmonary fibrosis was induced with 1.0 mL of one-off infusing silica suspension using the non-exposed intratracheal instillation (50 mg/mL/rat). In vivo transplantation of BMSCs-Exo effectively alleviated silica-induced pulmonary fibrosis, including a reduction in collagen accumulation, inhibition of TGF-β1, and decreased HYP content. Treatment of BMSCs-Exo increased the expression of epithelial marker proteins including E-cadherin (E-cad) and cytokeratin19 (CK19) and reduced the expression of fibrosis marker proteins including α-Smooth muscle actin (α-SMA) after exposure to silica suspension. Furthermore, we found that BMSCs-Exo inhibited the expression of Wnt/β-catenin pathway components (P-GSK3β, β-catenin, Cyclin D1) in pulmonary fibrosis tissue. BMSCs-Exo is involved in the alleviation of silica-induced pulmonary fibrosis by reducing the level of profibrotic factor TGF-β1 and inhibiting the progression of epithelial-mesenchymal transition (EMT). Additionally, attenuation of the Wnt/β-catenin signaling pathway closely related to EMT may be one of the mechanisms involved in anti-fibrotic effects of exosomes.

Keywords:

• Bone marrow mesenchymal stem/stromal cells
• exosomes
• pulmonary fibrosis
• silica
• EMT

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (NSFC) [grant numbers 81872575, 81602893, 81973089], Natural Science Foundation of Shandong Province [grant number ZR2015YL049]; Key Research and Development Plan of Shandong Province [grant number 2018GSF118018]; Medical and Health Technology Development Plan Project of Shandong Province [grant numbers 2016WS0540, 2018WSA18019]; Science and Technology Development Project of Traditional Chinese Medicine in Shandong Province [grant number 2019-0540]; Jinan Science and Technology Project [grant number 201907022]; Innovation Project of Shandong Academy of Medical Science and Academic Promotion Programme of Shandong First Medical University [grant number 2019QL001].