Abstract

Chitinase-3-like protein 1 (CHI3L1) is overexpressed in various types of diseases, particularly in sepsis, and contributes to disease progression. However, the role of CHI3L1 and the pathways involved in the progression of sepsis are not yet completely understood. In the present study, lipopolysaccharide (LPS) was used to construct mouse and cell models of sepsis. Reverse transcription-quantitative PCR was used to detect the expression of CHI3L1. Cycloheximide was used to analyze the protein stability of CHI3L1. The mRNA levels of CHI3L1 and the lactate content were found to be significantly elevated in the serum of patients with sepsis and in LPS-exposed RAW264.7 cells. Furthermore, LPS exposure significantly increased the lactylation of CHI3L1 in RAW264.7 cells. Lactate treatment promoted the lactylation of CHI3L1 and 2-DG treatment inhibited it. Lactylation induced the degradation of CHI3L1 protein. Furthermore, CHI3L1 knockdown inhibited macrophage apoptosis and the release of inflammatory cytokines (IL-1 β, IL-6 and TNF-α) and inactivated the NF-κB pathway in the LPS-exposed RAW264.7 cells. In addition, the analysis of the mouse model of sepsis revealed that knockdown of CHI3L1 reduced the IL-1 β, IL-6, TNF-α, creatinine, blood urea nitrogen, alanine transaminase, and aspartate aminotransferase levels, and attenuated damage induced by sepsis to the heart, liver, lung, and kidneys in mice with sepsis. On the whole, the present study demonstrates that the lactylation modification of CHI3L1 promotes the development of sepsis. Thus, focusing on CHI3L1 expression changes may prove to be a promising approach for the treatment of sepsis in the future.