Anti-Inflammatory, Antioxidant, and Antifibrotic Effects of Gingival-Derived MSCs on Bleomycin-Induced Pulmonary Fibrosis in Mice.

Xishuai Wang,Yang Gao,Weijun Guan,Shiyu Zhao,Junhui Lai

doi:10.3390/ijms23010099

Abstract

Background: Mesenchymal stem cell (MSC) intervention has been associated with lung protection. We attempted to determine whether mouse gingival-derived mesenchymal stem cells (GMSCs) could protect against bleomycin-induced pulmonary fibrosis. Methods: Mice were divided into three groups: control (Con), bleomycin (Bl), and bleomycin + MSCs (Bl + MSCs). Mice were treated with 5 mg/kg bleomycin via transtracheal instillation to induce pulmonary fibrosis. We assessed the following parameters: histopathological severity of injury in the lung, liver, kidney, and aortic tissues; the degree of pulmonary fibrosis; pulmonary inflammation; pulmonary oedema; profibrotic factor levels in bronchoalveolar lavage fluid (BALF) and lung tissue; oxidative stress-related indicators and apoptotic index in lung tissue; and gene expression levels of IL-1β, IL-8, TNF-α, lysophosphatidic acid (LPA), lysophosphatidic acid receptor 1 (LPA1), TGF-β, matrix metalloproteinase 9 (MMP-9), neutrophil elastase (NE), MPO, and IL-10 in lung tissue. Results: GMSC intervention attenuated bleomycin-induced pulmonary fibrosis, pulmonary inflammation, pulmonary oedema, and apoptosis. Bleomycin instillation notably increased expression levels of the IL-1β, IL-8, TNF-α, LPA, LPA1, TGF-β, MMP-9, NE, and MPO genes and attenuated expression levels of the IL-10 gene in lung tissue, and these effects were reversed by GMSC intervention. Bleomycin instillation notably upregulated MDA and MPO levels and downregulated GSH and SOD levels in lung tissue, and these effects were reversed by GMSC intervention. GMSC intervention prevented upregulation of neutrophil content in the lung, liver, and kidney tissues and the apoptotic index in lung tissue. Conclusions: GMSC intervention exhibits anti-inflammatory and antioxidant capacities. Deleterious accumulation of neutrophils, which is reduced by GMSC intervention, is a key component of bleomycin-induced pulmonary fibrosis. GMSC intervention impairs bleomycin-induced NE, MMP-9, LPA, APL1, and TGF-β release.

Highlights

Pulmonary fibrosis is characterised by shortness of breath, hypoxemia, and the accumulation of fixed fibrosis that leads to expiratory dyspnoea and is associated with unacceptably high incidence, representing a major healthcare problem with few available treatments [1,2]
gingival-derived mesenchymal stem cells (GMSCs) characteristics were similar to the properties of bone marrow- and adipose-derived Mesenchymal stem cell (MSC)
GMSCs can differentiate into neural cell lineages [16]

Summary

Introduction

Pulmonary fibrosis is characterised by shortness of breath, hypoxemia, and the accumulation of fixed fibrosis that leads to expiratory dyspnoea and is associated with unacceptably high incidence, representing a major healthcare problem with few available treatments [1,2]. GMSCs are used to treat skin diseases, peripheral nerve injuries, and oral and maxillofacial disorders It is both convenient and economical to separate gingival tissues from patients. We attempted to determine whether GMSC intervention could protect against bleomycin-induced pulmonary fibrosis. We attempted to determine whether mouse gingival-derived mesenchymal stem cells (GMSCs) could protect against bleomycin-induced pulmonary fibrosis. Bleomycin instillation notably increased expression levels of the IL-1β, IL-8, TNF-α, LPA, LPA1, TGF-β, MMP-9, NE, and MPO genes and attenuated expression levels of the IL-10 gene in lung tissue, and these effects were reversed by GMSC intervention. Bleomycin instillation notably upregulated MDA and MPO levels and downregulated GSH and SOD levels in lung tissue, and these effects were reversed by GMSC intervention. GMSC intervention impairs bleomycin-induced NE, MMP-9, LPA, APL1, and TGF-β release

Methods

Results

Conclusion