TM9SF1 knockdown decreases inflammation by enhancing autophagy in a mouse model of acute lung injury

Juan Xiao; Xiaofang Shen; Huabo Chen; Lu Ding; Ke Wang; Lihong Zhai; Chun Mao

doi:10.1016/j.heliyon.2022.e12092

TM9SF1 knockdown decreases inflammation by enhancing autophagy in a mouse model of acute lung injury

Heliyon. 2022 Dec 5;8(12):e12092. doi: 10.1016/j.heliyon.2022.e12092. eCollection 2022 Dec.

Authors

Juan Xiao¹, Xiaofang Shen¹, Huabo Chen¹, Lu Ding¹, Ke Wang¹, Lihong Zhai¹, Chun Mao¹

Affiliation

¹ Institute of Neuroscience and Brain Disease, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, No. 136, Jingzhou Street, Xiangyang, 441000, Hubei, China.

Abstract

TM9SF1 is a member of the TM9SF (Transmembrane 9 Superfamily Member) family, which usually has a long N-terminal extracellular region and nine transmembrane domains. TM9SF1's biological function and mechanisms in inflammation are yet unknown. Tm9sf1 was shown to be upregulated in the lung tissues of mice suffering from LPS-induced acute lung injury (ALI). Tm9sf1 knockout mice were studied, and it was shown that Tm9sf1 knockout significantly alleviated LPS-induced ALI, as evidenced by higher survival rate, improved pulmonary vascular permeability, decreased inflammatory cell infiltration, and downregulated inflammatory cytokines. TM9SF1 was also demonstrated to be a negative regulator of autophagy in the LPS-induced ALI model in vitro and in vivo. The autophagy inhibitor 3-MA could counteract the beneficial effects of Tm9sf1 knockout on ALI. Therefore, we discover for the first time the role and mechanism of TM9SF1 in LPS-induced ALI and establish a relationship between TM9SF1 regulated autophagy and ALI progression, which may provide novel targets for the treatment of ALI.

Keywords: ALI; Autophagy; Inflammation; TM9SF1.