4.7 Article

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

Journal

FASEB JOURNAL
Volume 34, Issue 8, Pages 10267-10285

Publisher

WILEY
DOI: 10.1096/fj.202000629R

Keywords

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

Funding

  1. NIH [R01HL136449, R01HL116597]
  2. National Center for Research Resources [UL1 RR024975-01]
  3. National Center for Advancing Translational Sciences [2 UL1 TR000445-06]
  4. University of Colorado [NCI P30 CA 46934-14, P30-CA046934 NCI]

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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 beta-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/beta-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.

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