The Impact of Selenium Deficiency and T-2 Toxin on Zip6 Expression in Kashin-Beck Disease.

Abstract

This study investigated the expression of Zip6, a gene predominantly located in the placenta, breast, and prostate tissues, in patients with Kashin-Beck disease (KBD). Environmental risk factor models for KBD were developed using low selenium (Se) feeding (with a Se content of 0.02 mg Se/kg in the feed) and exposure to T-2 toxin (200 ng/g*BW/D). Additionally, the study examined the alterations in Se and Zn²⁺ levels, along with the mRNA and protein expression levels of Zip6 and KBD related genes, including Mtf1, Mmp3, Mmp13, Adamts5, and Col2a1. Differentially expressed genes (DEGs) were examined by transcriptome sequencing to elucidate the mechanism by which Zip6 induces metabolic disorder of the extracellular matrix (ECM), subsequently leading to cartilage injury under the influence of Se deficiency and T-2 toxin. The findings indicated that the expression levels of Zip6 in adult and pediatric KBD chondrocytes were not synchronized. In the animal study, there was a notable increase in the Zn²⁺ level in the comprehensive exposure (CE) group. Moreover, in both the T-2 exposure (T-2) and CE groups, there was a significant decrease in the expression of Zip6 in each zone, and the expression of Adamts5 in the middle zone exhibited a significant increase (P < 0.05) correlating with varying degrees of cartilage tissue damage in each group. Sequencing results revealed that the significantly up-regulated DEGs in the CE group included Zimz2. This study suggested that Se and T-2 toxin may influence the expression of Zip6, and it investigated the role of Zn²⁺ in the pathogenesis of KBD, thereby providing a novel scientific foundation for understanding the pathogenesis of KBD.