The H 2 S-generating enzyme 3-mercaptopyruvate sulfurtransferase regulates pulmonary vascular smooth muscle cell migration and proliferation but does not impact normal or aberrant lung development

Nitric Oxide. 2021 Feb 1;107:31-45. doi: 10.1016/j.niox.2020.12.002. Epub 2020 Dec 15.

Abstract

Along with nitric oxide (NO), the gasotransmitters carbon monoxide (CO) and hydrogen sulfide (H2S) are emerging as potentially important players in newborn physiology, as mediators of newborn disease, and as new therapeutic modalities. Several recent studies have addressed H2S in particular in animal models of bronchopulmonary dysplasia (BPD), a common complication of preterm birth where oxygen toxicity stunts lung development. In those studies, exogenous H2S attenuated the impact of oxygen toxicity on lung development, and two H2S-generating enzymes were documented to affect pulmonary vascular development. H2S is directly generated endogenously by three enzymes, one of which, 3-mercaptopyruvate sulfurtransferase (MPST), has not been studied in the lung. In a hyperoxia-based animal model of BPD, oxygen exposure deregulated MPST expression during post-natal lung development, where MPST was localized to the smooth muscle layer of the pulmonary vessels in developing lungs. siRNA-mediated abrogation of MPST expression in human pulmonary artery smooth muscle cells in vitro limited baseline cell migration and cell proliferation, without affecting apoptosis or cell viability. In vivo, MPST was dispensable for normal lung development in Mpst-/-mice, and MPST did not contribute to stunted lung development driven by hyperoxia exposure, assessed by design-based stereology. These data demonstrate novel roles for MPST in pulmonary vascular smooth muscle cell physiology. The potential caveats of using Mpst-/- mice to study normal and aberrant lung development are also discussed, highlighting the possible confounding, compensatory effects of other H2S-generating enzymes that are present alongside MPST in the smooth muscle compartment of developing pulmonary vessels.

Keywords: Gasotransmitter; H(2)S; Hydrogen sulfide; Lung development; MPST; Smooth muscle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Cells, Cultured
  • Female
  • Gasotransmitters / metabolism*
  • Gene Expression / drug effects
  • Humans
  • Hydrogen Sulfide / metabolism*
  • Lung / cytology
  • Lung / metabolism*
  • Male
  • Mice, Inbred C57BL
  • Muscle, Smooth, Vascular / metabolism*
  • Organogenesis / physiology*
  • Sulfurtransferases / genetics
  • Sulfurtransferases / metabolism*

Substances

  • Gasotransmitters
  • Sulfurtransferases
  • 3-mercaptopyruvate sulphurtransferase
  • Hydrogen Sulfide