Dedicator of cytokinesis protein 2 knockdown ameliorates LPS-induced acute lung injury by modulating Rac1/2 activity

Yan Zhou; Wan Hu

doi:10.15586/aei.v50i3.543

Yan Zhou

Department of Respiratory Medicine, Third Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.

Wan Hu

Department of Respiratory and Critical Care Medicine, Zhuhai People’s Hospital, Zhuhai, Guangdong, P.R. China.

Keywords

acute lung injury, apoptosis, dedicator of cytokinesis protein 2, inflammation response, ras-related C3 botulinum toxin substrate 1/2

Abstract

Dedicator of cytokinesis protein 2 (DOCK2) is a member of the cytoskeletal dynamics protein family, and is ubiquitously expressed in hematopoietic cells according to previous studies. This paper was intended to explore the underlying mechanism that DOCK2 might involve in the progression of acute lung injury (ALI). Following lipopolysaccharide (LPS) induction in the purchased A549 cells, the expression level of DOCK2 was determined and its knockdown was performed by transfection. Subsequently, the viability, inflammation, oxidative stress barrier, and apoptosis of transfected A549 cells were measured to observe the alterations. Inflammation-related and apoptosis-related proteins were measured by western blot analysis. Finally, 8-Chlorophenylthio-cyclic monophosphate (8-CPT), ras-related C3 botulinum toxin substrate (Rac) 1 agonist, was applied to treat cells for investigating the underlying mechanism regarding the role of DOCK2. According to the results, DOCK2 was upregulated in LPS-induced A549 cells. Following the knockdown of DOCK2, the release of inflammatory cytokines was alleviated, accompanied by attenuated oxidative stress, barrier injury, and apoptosis of LPS-induced A549 cells. Nonetheless, this trend was reversed by further treatment of 8-CPT. In summary, DOCK2 knockdown alleviates inflammation, oxidative stress, barrier injury, and apoptosis of LPS-induced A549 cells by associating with Rac1/Rac2. These findings highlighted the therapeutic potential of DOCK2 for the treatment of ALI.

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