Dermatopontin is a novel regulator of the CdCl2-induced decrease in claudin-11 expression

Abstract

Cadmium (Cd) is a ubiquitous environmental heavy metal, which may be harmful to the reproductive functions through injury to the blood-testis barrier (BTB). However, the underlying mechanism of this adverse effect on the BTB remains uncharacterized. A preliminary study revealed that dermatopontin (DPT) expression was significantly increased in Cd chloride (CdCl2)-treated Sertoli cells in vitro, which suggested that an increase in DPT expression is crucial for CdCl2-induced BTB damage. To explore this further, in the present study we initially determined that DPT is expressed in testis Sertoli cells. The treatment of cells with CdCl2 resulted in a significant increase in DPT expression and a parallel decrease in claudin-11 expression, both in vivo and in vitro. To confirm the relationship between DPT and claudin-11, a DPT-silenced 15P-1 Sertoli cell model was established. We determined that DPT silencing could partly reduce the CdCl2-induced decrease in claudin-11 expression. Additionally, western blot analyses demonstrated that the p38 signaling pathway is involved in the effect of CdCl2 on DPT expression. In conclusion, the present study provides the first evidence that DPT may be a novel effector of CdCl2, highlighting the significant role of DPT in the regulation of claudin-11 expression.

Keywords: Blood-testis barrier; CdCl(2); Claudin-11; Dermatopontin.