%0 Journal Article
%A He, Hao
%A Yang, Wu
%A Su, Nan
%A Zhang, Chuankai
%A Dai, Jianing
%A Han, Feng
%A Singhal, Mahak
%A Bai, Wenjuan
%A Zhu, Xiaolan
%A Zhu, Jing
%A Liu, Zhen
%A Xia, Wencheng
%A Liu, Xiaoting
%A Zhang, Chonghe
%A Jiang, Kai
%A Huang, Wenhui
%A Chen, Dan
%A Wang, Zhaoyin
%A He, Xueyang
%A Kirchhoff, Frank
%A Li, Zhenyu
%A Liu, Cong
%A Huan, Jingning
%A Wang, Xiaohong
%A Wei, Wu
%A Wang, Jing
%A Augustin, Hellmut
%A Hu, Junhao
%T Activating NO-sGC crosstalk in the mouse vascular niche promotes vascular integrity and mitigates acute lung injury.
%J Journal of experimental medicine
%V 220
%N 2
%@ 0022-1007
%C New York, NY
%I Rockefeller Univ. Press
%M DKFZ-2022-02818
%P e20211422
%D 2023
%Z DKFZ-ZMBH Alliance
%X 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.
%K Mice
%K Animals
%K Soluble Guanylyl Cyclase: genetics
%K Soluble Guanylyl Cyclase: metabolism
%K Pericytes
%K Nitric Oxide: metabolism
%K Lipopolysaccharides: pharmacology
%K Acute Lung Injury: genetics
%K Acute Lung Injury: metabolism
%K Soluble Guanylyl Cyclase (NLM Chemicals)
%K Nitric Oxide (NLM Chemicals)
%K Lipopolysaccharides (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:36350314
%R 10.1084/jem.20211422
%U https://inrepo02.dkfz.de/record/182641