Science and Research

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

Along with nitric oxide (NO), the gasotransmitters carbon monoxide (CO) and hydrogen sulfide (H(2)S) are emerging as potentially important players in newborn physiology, as mediators of newborn disease, and as new therapeutic modalities. Several recent studies have addressed H(2)S 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 H(2)S attenuated the impact of oxygen toxicity on lung development, and two H(2)S-generating enzymes were documented to affect pulmonary vascular development. H(2)S 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 H(2)S-generating enzymes that are present alongside MPST in the smooth muscle compartment of developing pulmonary vessels.

  • Lignelli, E.
  • Palumbo, F.
  • Bayindir, S. G.
  • Nagahara, N.
  • Vadász, I.
  • Herold, S.
  • Seeger, W.
  • Morty, R. E.

Keywords

  • Animals
  • Animals, Newborn
  • Cell Movement/physiology
  • Cell Proliferation/physiology
  • Cells, Cultured
  • Female
  • Gasotransmitters/*metabolism
  • Gene Expression/drug effects
  • Humans
  • Hydrogen Sulfide/*metabolism
  • Lung/cytology/*metabolism
  • Male
  • Mice, Inbred C57BL
  • Muscle, Smooth, Vascular/*metabolism
  • Organogenesis/*physiology
  • Sulfurtransferases/genetics/*metabolism
  • *Gasotransmitter
  • *h(2)s
  • *Hydrogen sulfide
  • *Lung development
  • *mpst
  • *Smooth muscle
Publication details
DOI: 10.1016/j.niox.2020.12.002
Journal: Nitric Oxide
Pages: 31-45 
Work Type: Original
Location: UGMLC
Disease Area: DPLD
Partner / Member: JLU, MPI-BN
Access-Number: 33338600

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