Activating NO-sGC crosstalk in the mouse vascular niche promotes vascular integrity and mitigates acute lung injury. Academic Article uri icon


  • 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.

published proceedings

  • J Exp Med

altmetric score

  • 14.85

author list (cited authors)

  • He, H., Yang, W. u., Su, N., Zhang, C., Dai, J., Han, F., ... Hu, J.

citation count

  • 0

complete list of authors

  • He, Hao||Yang, Wu||Su, Nan||Zhang, Chuankai||Dai, Jianing||Han, Feng||Singhal, Mahak||Bai, Wenjuan||Zhu, Xiaolan||Zhu, Jing||Liu, Zhen||Xia, Wencheng||Liu, Xiaoting||Zhang, Chonghe||Jiang, Kai||Huang, Wenhui||Chen, Dan||Wang, Zhaoyin||He, Xueyang||Kirchhoff, Frank||Li, Zhenyu||Liu, Cong||Huan, Jingning||Wang, Xiaohong||Wei, Wu||Wang, Jing||Augustin, Hellmut G||Hu, Junhao

publication date

  • February 2023