Resident mesenchymal vascular progenitors modulate adaptive angiogenesis and pulmonary remodeling via regulation of canonical Wnt signaling

Megan E. Summers, Bradley W. Richmond, Swapna Menon, Ryan M. Sheridan, Jonathan A. Kropski, Sarah A. Majka, M. Mark Taketo, Julie A. Bastarache, James D. West, Stijn De Langhe, Patrick Geraghty, Dwight J. Klemm, Hong Wei Chu, Rachel S. Friedman, Yuankai K. Tao, Robert F. Foronjy, Susan M. Majka

Research output: Contribution to journalArticlepeer-review

Abstract

Adaptive angiogenesis is necessary for tissue repair, however, it may also be associated with the exacerbation of injury and development of chronic disease. In these studies, we demonstrate that lung mesenchymal vascular progenitor cells (MVPC) modulate adaptive angiogenesis via lineage trace, depletion of MVPC, and modulation of β-catenin expression. Single cell sequencing confirmed MVPC as multipotential vascular progenitors, thus, genetic depletion resulted in alveolar simplification with reduced adaptive angiogenesis. Following vascular endothelial injury, Wnt activation in MVPC was sufficient to elicit an emphysema-like phenotype characterized by increased MLI, fibrosis, and MVPC driven adaptive angiogenesis. Lastly, activation of Wnt/β-catenin signaling skewed the profile of human and murine MVPC toward an adaptive phenotype. These data suggest that lung MVPC drive angiogenesis in response to injury and regulate the microvascular niche as well as subsequent distal lung tissue architecture via Wnt signaling.

Original languageEnglish (US)
Pages (from-to)10267-10285
Number of pages19
JournalFASEB Journal
Volume34
Issue number8
DOIs
StatePublished - Aug 1 2020

Keywords

  • adaptive angiogenesis
  • emphysema
  • mesenchymal vascular progenitor cell
  • microvascular niche
  • Wnt signaling

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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