Study on the Role of VE-cadherin/c-Abl Complex in Ang II-Associated Lung Injury

Abstract

Our previous study found that Ang II-associated pulmonary microvascular endothelial cell apoptosis and skeletal remodeling are the main mechanisms leading to the impaired pulmonary microvascular endothelial dysfunction and leading to a series of disease-associated lung injury. Therefore, the purpose of this study is to explore the role of VE-cadherin/c-Abl complex in Ang II-associated lung injury. We constructed Ang II-associated lung injury models in vivo and in vitro. We found that in the Ang II-associated lung injury model, pulmonary microvascular endothelial cell apoptosis increased, cytoskeleton rearrangement, pVE-cadherin dephosphorylation, VE-cadherin/c-Abl complex depolymerization, and c-Abl expression increased then transfer to nucleus. After overexpression of c-Abl, although it cannot directly lead to pulmonary microvascular endothelial cells(PMVEC) apoptosis and cytoskeleton rearrangement, it improves the sensitivity of PMVEC to Ang II-associated apoptosis and backbone rearrangement. After inhibiting the expression of c-Abl, PMVEC apoptosis was reduced and cytoskeleton rearrangement was inhibited, partially reversing the Ang II-associated lung injury. The above results indicate that the VE-cadherin/c-Abl complex plays a protective role in Ang II-associated lung injury. Funding: This work is funded by the National Natural Science Foundation of Hubei Province (Grant No.2019CFB469) Declaration of Interest: The authors declare that they have no competing interests. Ethical Approval: The Ethical Committee of Renmin Hospital of Wuhan University approved the animal study protocol.