The protective effect of hydrogen sulfide on systemic sclerosis associated skin and lung fibrosis in mice model

Zhi Wang,Kai Song,Ying Lu,Luyan Gao,Huaying Shen,Xiaoya Yin,Sheng Feng,Lingyun Li

doi:10.1186/s40064-016-2774-4

Abstract

BackgroudSystemic sclerosis (SSc) caused fibrosis can be fatal and it still lack of effective treatment. Hydrogen sulfide (H2S) appears to be an attractive therapeutic candidates. This study aimed to investigate the protective effect of H2S on SSc-associated skin and lung fibrosis.Methods We developed a model of SSc by subcutaneous injecting BLM to female C3H mice. The mice received daily subcutaneous injections of NaHS (56 and 112 μg/kg), an H2S donor. On days 7, 28, and 42, the mice were killed and blood samples were collected to measure the plasma H2S concentration, the skin and lung tissues was harvested for microscopic examination, immunohistochemistry and quantify biological parameters (hydroxyproline content, RT-qPCR and Western blot).ResultsIn model group, the dermis of skin tissues at different time points gradually thickened, collagen deposition increased. The lung tissues presented pathological changes such as obvious inflammatory cell infiltration, increased collagen deposition and the plasma H2S concentrations points significantly decreased. Administration of NaHS markedly decreased the biomarkers of fibrosis such as α-smooth muscle actin, collagen-I, collagen-III, fibronectin, transforming growth factor-β1, Smad2/3 phosphorylation and inflammation including the marker protein of monocyte/macrophage and monocyte chemoattractant protein-1 in the lung. Compared to the low dose group, the expression in the high dose group have decreased trend, but the difference was not significant.ConclusionWe demonstrate the beneficial effects of H2S on SSc-associated skin and lung fibrosis. H2S may be a potential therapy against this intractable disease.

Highlights

Systemic sclerosis (SSc) is a severe connective tissue disease of unknown etiology
Thereinto, the inflammatory cell infiltration was more evident in the 7-day group (Fig. 1j); whereas the alveolar collapse, patchy fusion, collagen deposition, and pulmonary parenchymal fibrosis were the more evident in the 28- and 42-day group (Fig. 1o, p)
After NaHS intervention, lung tissue pathological changes in mice from the treatment group were significantly relieved, inflammatory cell filtration and collagen deposition decreased, alveolar structure improved, the alveoli were more transparent and bright, and the degree of inflammation and fibrosis decreased on 7-day (Fig. 3c, d) and on 42 day (Fig. 3h, i; m, n)

Summary

Introduction

Systemic sclerosis (SSc) is a severe connective tissue disease of unknown etiology. SSc is characterized by multivisceral fibrosis resulting from inflammation, vascular injury and excessive collagen deposition. Skin sclerosis can cause discomfort and organ involvements—such as pulmonary fibrosis—can be fatal. The mechanisms of fibrosis in SSc have not been fully elucidated. Hydrogen sulfide (H2S) is a newly recognized endogenous gasotransmitter analogic to nitric oxide and carbon monoxide (Wang 2012). As a new emerging gaseous signalling molecule, for a long time, its study was limited to its toxicity. In the 1990s, it was discovered that endogenous H2S participated in anti-inflammation, anti-oxidation, and the regulation of cell proliferation and apoptosis (Gao et al 2012; Moody and Calvert 2011; Vandiver and Snyder 2012).

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