Selenium deficiency caused hepatitis in chickens via the miR-138-5p/SelM/ROS/Ca2+ overload pathway induced by hepatocyte necroptosis.

Abstract

Selenoprotein M (SelM), a key thioredoxin like enzyme in the endoplasmic reticulum (ER), is closely related to hepatocyte degeneration. However, the role of miR-138-5p/SelM and necroptosis in chicken SelM-deficient hepatitis and the specific biological mechanism of liver inflammation caused by SelM deficiency have not been elucidated. We established an in vivo chicken liver Se deficiency model by feeding a low-Se diet. The miR-138-5p knockdown and overexpression models and SelM knockdown models were established in LMH cells for an in vitro study. Transmission electron microscopy, H&E staining, Fluo4-AM/ER staining, and flow cytometry were used to detect the morphological changes in chicken liver tissue and the expression changes of necroptosis and inflammation in chicken liver cells. We observed that Se deficiency resulted in liver inflammation, up-regulation of miR-138-5p expression and down-regulation of SelM expression in chickens. Oxidative stress, Ca2+ overload, energy metabolism disorder and necroptosis occurred in chicken liver tissue. Importantly, ROS and the Ca2+ inhibitor could effectively alleviate the energy metabolism disorder, necroptosis and inflammatory cytokine secretion caused by miR-138-5p overexpression and SelM knockdown in LMH cells. In conclusion, selenium deficiency causes hepatitis by upregulating miR-138-5p targeting SelM. Our research findings enrich our knowledge about the biological functions of SelM and provide a theoretical basis for the lack of SelM leading to liver inflammation in chickens.