Vascular dysfunction in aged mice contributes to persistent lung fibrosis.

Aging Cell
Nunzia CaporarelloGiovanni Ligresti

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive disease thought to result from impaired lung repair following injury and is strongly associated with aging. While vascular alterations have been associated with IPF previously, the contribution of lung vasculature during injury resolution and fibrosis is not well understood. To compare the role of endothelial cells (ECs) in resolving and non-resolving models of lung fibrosis, we applied bleomycin intratracheally to young and aged mice. We found that injury in aged mice elicited capillary rarefaction, while injury in young mice resulted in increased capillary density. ECs from the lungs of injured aged mice relative to young mice demonstrated elevated pro-fibrotic and reduced vascular homeostasis gene expression. Among the latter, Nos3 (encoding the enzyme endothelial nitric oxide synthase, eNOS) was transiently upregulated in lung ECs from young but not aged mice following injury. Young mice deficient in eNOS recapitulated the non-resolving lung fibrosis observed in aged animals following injury, suggesting that eNOS directly participates in lung fibrosis resolution. Activation of the NO receptor soluble guanylate cyclase in human lung fibroblasts reduced TGFβ-induced pro-fib...Continue Reading

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Citations

Dec 3, 2020·Experimental & Molecular Medicine·Benjamin NgSebastian Schafer
Jan 26, 2021·American Journal of Respiratory Cell and Molecular Biology·Qi TanDaniel J Tschumperlin
May 26, 2021·The American Journal of Pathology·Roberto F NicosiaDomenico Ribatti

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Methods Mentioned

BETA
FACS
dissection
profiler
PCR
SMA

Software Mentioned

ARRIVE
GraphPad Prism

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