PKD2/polycystin-2 inhibits LPS-induced acute lung injury in vitro and in vivo by activating autophagy

BMC Pulmonary Medicine

Research

Kaixuan Wu¹  Lina Bu¹  Fan Pan¹  Xiaotao Xu¹  Aizhong Wang¹ 

[1]Department of Anesthesiology, Affiliated Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University, 200233, Shanghai, China

关键词: Polycystin-2;    Acute lung injury;    Inflammation;    Autophagy;    LPS;   

DOI  :  10.1186/s12890-023-02449-w

 received in 2022-09-11, accepted in 2023-04-21,  发布年份 2023

来源: Springer

【 摘 要 】

Polycystin-2 (PC2), which is a transmembrane protein encoded by the PKD2 gene, plays an important role in kidney disease, but its role in lipopolysaccharide (LPS)-induced acute lung injury (ALI) is unclear. We overexpressed PKD2 in lung epithelial cells in vitro and in vivo and examined the role of PKD2 in the inflammatory response induced by LPS in vitro and in vivo. Overexpression of PKD2 significantly decreased production of the inflammatory factors TNF-α, IL-1β, and IL-6 in LPS-treated lung epithelial cells. Moreover, pretreatment with 3-methyladenine (3-MA), an autophagy inhibitor, reversed the inhibitory effect of PKD2 overexpression on the secretion of inflammatory factors in LPS-treated lung epithelial cells. We further demonstrated that overexpression of PKD2 could inhibit LPS-induced downregulation of the LC3BII protein levels and upregulation of SQSTM1/P62 protein levels in lung epithelial cells. Moreover, we found that LPS-induced changes in the lung wet/dry (W/D) weight ratio and levels of the inflammatory cytokines TNF-α, IL-6 and IL-1β in the lung tissue were significantly decreased in mice whose alveolar epithelial cells overexpressed PKD2. However, the protective effects of PKD2 overexpression against LPS-induced ALI were reversed by 3-MA pretreatment. Our study suggests that overexpression of PKD2 in the epithelium may alleviate LPS-induced ALI by activating autophagy.

【 授权许可】

CC BY   
© The Author(s) 2023

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