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@ARTICLE{He:182641,
author = {H. He and W. Yang and N. Su and C. Zhang and J. Dai and F.
Han and M. Singhal and W. Bai and X. Zhu and J. Zhu and Z.
Liu and W. Xia and X. Liu and C. Zhang and K. Jiang and W.
Huang and D. Chen and Z. Wang and X. He and F. Kirchhoff and
Z. Li and C. Liu and J. Huan and X. Wang and W. Wei and J.
Wang and H. Augustin$^*$ and J. Hu},
title = {{A}ctivating {NO}-s{GC} crosstalk in the mouse vascular
niche promotes vascular integrity and mitigates acute lung
injury.},
journal = {Journal of experimental medicine},
volume = {220},
number = {2},
issn = {0022-1007},
address = {New York, NY},
publisher = {Rockefeller Univ. Press},
reportid = {DKFZ-2022-02818},
pages = {e20211422},
year = {2023},
note = {DKFZ-ZMBH Alliance},
abstract = {Disruption of endothelial cell (ECs) and pericytes
interactions results in vascular leakage in acute lung
injury (ALI). However, molecular signals mediating
EC-pericyte crosstalk have not been systemically
investigated, and whether targeting such crosstalk could be
adopted to combat ALI remains elusive. Using comparative
genome-wide EC-pericyte crosstalk analysis of healthy and
LPS-challenged lungs, we discovered that crosstalk between
endothelial nitric oxide and pericyte soluble guanylate
cyclase (NO-sGC) is impaired in ALI. Indeed, stimulating the
NO-sGC pathway promotes vascular integrity and reduces lung
edema and inflammation-induced lung injury, while
pericyte-specific sGC knockout abolishes this protective
effect. Mechanistically, sGC activation suppresses
cytoskeleton rearrangement in pericytes through inhibiting
VASP-dependent F-actin formation and MRTFA/SRF-dependent de
novo synthesis of genes associated with cytoskeleton
rearrangement, thereby leading to the stabilization of
EC-pericyte interactions. Collectively, our data demonstrate
that impaired NO-sGC crosstalk in the vascular niche results
in elevated vascular permeability, and pharmacological
activation of this crosstalk represents a promising
translational therapy for ALI.},
keywords = {Mice / Animals / Soluble Guanylyl Cyclase: genetics /
Soluble Guanylyl Cyclase: metabolism / Pericytes / Nitric
Oxide: metabolism / Lipopolysaccharides: pharmacology /
Acute Lung Injury: genetics / Acute Lung Injury: metabolism
/ Soluble Guanylyl Cyclase (NLM Chemicals) / Nitric Oxide
(NLM Chemicals) / Lipopolysaccharides (NLM Chemicals)},
cin = {A190},
ddc = {610},
cid = {I:(DE-He78)A190-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36350314},
doi = {10.1084/jem.20211422},
url = {https://inrepo02.dkfz.de/record/182641},
}