Endothelial-Derived Angiocrine Signals Induce and Sustain Regenerative Lung Alveolarization

@article{Ding2011EndothelialDerivedAS,
  title={Endothelial-Derived Angiocrine Signals Induce and Sustain Regenerative Lung Alveolarization},
  author={B. Ding and D. Nolan and P. Guo and Alexander O. Babazadeh and Zhongwei Cao and Z. Rosenwaks and R. Crystal and M. Simons and Thomas N. Sato and S. Worgall and K. Shido and S. Rabbany and S. Rafii},
  journal={Cell},
  year={2011},
  volume={147},
  pages={539-553}
}
To identify pathways involved in adult lung regeneration, we employ a unilateral pneumonectomy (PNX) model that promotes regenerative alveolarization in the remaining intact lung. We show that PNX stimulates pulmonary capillary endothelial cells (PCECs) to produce angiocrine growth factors that induce proliferation of epithelial progenitor cells supporting alveologenesis. Endothelial cells trigger expansion of cocultured epithelial cells, forming three-dimensional angiospheres reminiscent of… Expand
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References

SHOWING 1-10 OF 83 REFERENCES
Inductive angiocrine signals from sinusoidal endothelium are required for liver regeneration
TLDR
It is shown that inducible genetic ablation of vascular endothelial growth factor (VEGF)-A receptor-2 (VEGFR2) in the LSECs impairs the initial burst of hepatocyte proliferation and subsequent reconstitution of the hepatovascular mass by inhibiting upregulation of the endothelial-cell-specific transcription factor Id1, which suggests an instructive vascular niche in the early phases of physiological liver regeneration. Expand
Epithelial-vascular cross talk mediated by VEGF-A and HGF signaling directs primary septae formation during distal lung morphogenesis.
TLDR
Particles of the molecular cross talk between respiratory epithelial cells and pulmonary capillaries necessary for the formation of the gas exchange surface of the lung are identified and Hgf is identified as a putative endothelium-derived factor that mediates the reciprocal signaling from the vasculature to the respiratory epithelium. Expand
Targeted Induction of Lung Endothelial Cell Apoptosis Causes Emphysema-like Changes in the Mouse*S⃞
TLDR
It is shown that targeted ablation of lung capillary endothelial cells recapitulates the cellular events involved in cigarette smoke-induced emphysema, one of the most prevalent nonneoplastic lung diseases. Expand
FGF9 and SHH regulate mesenchymal Vegfa expression and development of the pulmonary capillary network
TLDR
It is shown that fibroblast growth factor 9 (FGF9) and sonic hedgehog (SHH) signaling to lung mesenchyme, but not to endothelial cells, are each necessary and together sufficient for distal capillary development. Expand
A Gata6-Wnt pathway required for epithelial stem cell development and airway regeneration
TLDR
It is demonstrated that Gata6-regulated Wnt signaling controls the balance between progenitor expansion and epithelial differentiation required for both lung development and regeneration. Expand
Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis
TLDR
It is shown with genetic experiments in mouse and zebrafish that ephrin-B2, a transmembrane ligand for Eph receptor tyrosine kinases, promotes sprouting behaviour and motility in the angiogenic endothelium, and shows that full VEGFR3 signalling is coupled to receptor internalization. Expand
Epithelial-mesenchymal interactions in pulmonary fibrosis.
  • H. Chapman
  • Biology, Medicine
  • Annual review of physiology
  • 2011
TLDR
Understanding specific signaling mechanisms driving the mesenchymal response to TGF β1 may reveal therapeutics to attenuate fibrogenesis yet preserve the important homeostatic functions of TGFβ1. Expand
Integrin α6β4 identifies an adult distal lung epithelial population with regenerative potential in mice.
TLDR
The finding that a previously unrecognized subpopulation of mouse alveolar epithelial cells expressing the laminin receptor α6β4, but little or no pro-surfactant C (pro-SPC), is endowed with regenerative potential is reported, supporting the idea that there is a stable AEC progenitor population in the adult lung. Expand
VEGF is deposited in the subepithelial matrix at the leading edge of branching airways and stimulates neovascularization in the murine embryonic lung
TLDR
The restricted temporal and spatial expression of V EGF suggests that matrix‐associated VEGF links airway branching with blood vessel formation by stimulating neovascularization at the leading edge of branching airways. Expand
Angiocrine factors from Akt-activated endothelial cells balance self-renewal and differentiation of haematopoietic stem cells
TLDR
It is demonstrated that Akt activation in endothelial cells, through recruitment of mTOR, but not the FoxO pathway, upregulates specific angiocrine factors that support expansion of CD34−Flt3− KLS HSPCs with long-term haematopoietic stem cell (LT-HSC) repopulation capacity. Expand
...
1
2
3
4
5
...