Hydrogen Sulfide as a Potential Therapeutic Target in Fibrosis

Hydrogen sulfide (H(2)S), produced endogenously by the activation of two major H(2)S-generating enzymes (cystathionine β-synthase and cystathionine γ-lyase), plays important regulatory roles in different physiologic and pathologic conditions. The abnormal metabolism of H(2)S is associated with fibrosis pathogenesis, causing damage in structure and function of different organs. A number of in vivo and in vitro studies have shown that both endogenous H(2)S level and the expressions of H(2)S-generating enzymes in plasma and tissues are significantly downregulated during fibrosis. Supplement with exogenous H(2)S mitigates the severity of fibrosis in various experimental animal models. The protective role of H(2)S in the development of fibrosis is primarily attributed to its antioxidation, antiapoptosis, anti-inflammation, proangiogenesis, and inhibition of fibroblasts activities. Future studies might focus on the potential to intervene fibrosis by targeting the pathway of endogenous H(2)S-producing enzymes and H(2)S itself.