Understanding hydrogen sulfide signaling in neonatal airway disease

Abstract

Introduction: Airway dysfunction leading to chronic lung disease is a common consequence of premature birth and mechanisms responsible for early and progressive airway remodeling are not completely understood. Current therapeutic options are only partially effective in reducing the burden of neonatal airway disease and premature decline of lung function. Gasotransmitter hydrogen sulfide (H₂S) has been recently recognized for its therapeutic potential in lung diseases.

Areas covered: Contradictory to its well-known toxicity at high concentrations, H₂S has been characterized to have anti-inflammatory, antioxidant, and antiapoptotic properties at physiological concentrations. In the respiratory system, endogenous H₂S production participates in late lung development and exogenous H₂S administration has a protective role in a variety of diseases such as acute lung injury and chronic pulmonary hypertension and fibrosis. Literature searches performed using NCBI PubMed without publication date limitations were used to construct this review, which highlights the dichotomous role of H₂S in the lung, and explores its promising beneficial effects in lung diseases.

Expert opinion: The emerging role of H₂S in pathways involved in chronic lung disease of prematurity along with its recent use in animal models of BPD highlight H₂S as a potential novel candidate in protecting lung function following preterm birth.

Keywords: Bronchopulmonary dysplasia; hydrogen sulfide; lung development; neonatal airway disease; prematurity.

Figure 1.. H₂S and its potential therapeutic role in the developing airway.

Premature birth is a deleterious insult to premature lungs, along with various interventions necessary for survival that can unfortunately cause life-long diseases of the airway. Considering the multitude of H₂S targets that overlap with pathways involved in lung physiology and disease, this gasotransmitter is deserving of more research into its role in the developing airway. Portions of this figure were prepared using the Motifolio Scientific Illustration Toolkits. Abbreviations used in the figure: 3-MST, 3-mercaptopyruvate sulfurtransferase; CAT, cysteine aminotransferase; CBS, cystathionine ß synthase; CSE, cystathionine gamma lyase; EMT, epithelial-mesenchymal transition; ER, endoplasmic reticulum; GSH, glutathione; H₂S, hydrogen sulfide; iNOS, inducible nitric oxide synthase; K_ATP, ATP-sensitive K⁺ channel; mPAP, mean pulmonary arterial pressure; NO, nitric oxide; ROS, reactive oxygen species; SMC, smooth muscle cell; SOD, superoxide dismutase.