Chitinase 3-like 1 overexpression aggravates hypoxia-reoxygenation injury in IEC-6 cells by inhibiting the PI3K/AKT signalling pathway.

Abstract

Intestinal ischaemia-reperfusion (I/R) is a common clinical pathology with high incidence and mortality rates. However, the mechanisms underlying intestinal I/R injury remain unclear. In this study, we investigated the role and mechanism of chitinase 3-like 1 (CHI3L1) during intestinal I/R injury. Therefore, we analysed the expression levels of CHI3L1 in the intestinal tissue of an intestinal I/R rat model and explored its effects and mechanism in a hypoxia-reoxygenation (H/R) IEC-6 cell model. We found that intestinal I/R injury elevated CHI3L1 levels in the serum, ileum and duodenum, whereas H/R enhanced CHI3L1 expression in IEC-6 cells. The H/R-induced inhibition of proliferation and apoptosis was alleviated by CHI3L1 knockdown and aggravated by CHI3L1 overexpression. In addition, CHI3L1 knockdown alleviated, and CHI3L1 overexpression aggravated, the H/R-induced inflammatory response and oxidative stress. Mechanistically, CHI3L1 overexpression weakened the activation of the phosphoinositide 3-kinase (PI3K)/AKT pathway, suppressed the nuclear translocation of Nrf2, and promoted the nuclear translocation of nuclear factor κB (NF-κB). Moreover, CHI3L1 knockdown had the opposite effect on the PI3K/AKT pathway, Nrf2, and NF-κB. Moreover, the PI3K inhibitor LY294002 blocked the effect of CHI3L1 knockdown on the H/R-induced inhibition of proliferation, apoptosis, inflammatory response and oxidative stress. In conclusion, CHI3L1 expression was induced during intestinal I/R and H/R injury in IEC-6 cells, and CHI3L1 overexpression aggravated H/R injury in IEC-6 cells by inhibiting the PI3K/AKT signalling pathway. Therefore, CHI3L1 may be an effective target for controlling intestinal I/R injury.