Platelet-derived SDF-1 primes the pulmonary capillary vascular niche to drive lung alveolar regeneration. Academic Article uri icon

Overview

MeSH

  • Animals
  • Antigens, CD
  • Cadherins
  • Endothelial Cells
  • Epidermal Growth Factor
  • Gene Deletion
  • Ligands
  • Matrix Metalloproteinase 14
  • Mice
  • Organ Specificity
  • Platelet Membrane Glycoprotein IIb
  • Pneumonectomy
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptors, CXCR
  • Receptors, CXCR4
  • Signal Transduction
  • Thrombopoietin
  • Vascular Endothelial Growth Factor Receptor-2

MeSH Major

  • Blood Platelets
  • Capillaries
  • Chemokine CXCL12
  • Pulmonary Alveoli
  • Regeneration

abstract

  • The lung alveoli regenerate after surgical removal of the left lobe by pneumonectomy (PNX). How this alveolar regrowth/regeneration is initiated remains unknown. We found that platelets trigger lung regeneration by supplying stromal-cell-derived factor-1 (SDF-1, also known as CXCL12). After PNX, activated platelets stimulate SDF-1 receptors CXCR4 and CXCR7 on pulmonary capillary endothelial cells (PCECs) to deploy the angiocrine membrane-type metalloproteinase MMP14, stimulating alveolar epithelial cell (AEC) expansion and neo-alveolarization. In mice lacking platelets or platelet Sdf1, PNX-induced alveologenesis was diminished. Reciprocally, infusion of Sdf1(+/+) but not Sdf1-deficient platelets rescued lung regeneration in platelet-depleted mice. Endothelial-specific ablation of Cxcr4 and Cxcr7 in adult mice similarly impeded lung regeneration. Notably, mice with endothelial-specific Mmp14 deletion exhibited impaired expansion of AECs but not PCECs after PNX, which was not rescued by platelet infusion. Therefore, platelets prime PCECs to initiate lung regeneration, extending beyond their haemostatic contribution. Therapeutic targeting of this haemo-vascular niche could enable regenerative therapy for lung diseases.

publication date

  • February 2015

has subject area

  • Animals
  • Antigens, CD
  • Blood Platelets
  • Cadherins
  • Capillaries
  • Chemokine CXCL12
  • Endothelial Cells
  • Epidermal Growth Factor
  • Gene Deletion
  • Ligands
  • Matrix Metalloproteinase 14
  • Mice
  • Organ Specificity
  • Platelet Membrane Glycoprotein IIb
  • Pneumonectomy
  • Pulmonary Alveoli
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptors, CXCR
  • Receptors, CXCR4
  • Regeneration
  • Signal Transduction
  • Thrombopoietin
  • Vascular Endothelial Growth Factor Receptor-2

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4886751

Digital Object Identifier (DOI)

  • 10.1038/ncb3096

PubMed ID

  • 25621952

Additional Document Info

start page

  • 123

end page

  • 136

volume

  • 17

number

  • 2