Molecular characterization and expression analysis of the regenerating islet-derived protein 3 alpha from Suncus murinus

The regenerating islet-derived protein (Reg) 3 family of C-type lectins is primarily produced in the intestinal epithelial cells and exert several different physiological functions including as antimicrobial agents. The Reg3 family includes Reg3 alpha, Reg3 beta, Reg3 gamma, and Reg3 delta in mice, while only Reg3 alpha and Reg3 gamma are found in humans. Accumulating evidence suggests that Reg3 proteins play several critical roles in maintaining host-bacterial homeostasis in the mammalian intestine, but little information is available on the mechanism regulating their expression in other organisms. In an effort to gain some insight into the evolutionary features of Reg3 proteins in mammals, we cloned Reg3 alpha from suncus (Suncus murinus), which belongs to the Insectivora, and examined the tissue specific gene expression of Reg3 alpha. Although suncus Reg3 alpha lacks the bacterial binding/killing motifs, the deduced peptide of Reg3 alpha do exhibit the other characteristic features of Reg3 family members, including several disulfide bonds and trypsin-dependent proteolytic processing, suggesting their functionality. Reg3 alpha mRNA was found to be most abundant in the pancreas and highly expressed in the intestine. Reg3 alpha function is not limited to its bactericidal effect; it is also known to attenuate intestinal inflammation. Given that the expression of Reg3a alpha mRNA in DSS-treated suncus was significantly greater than that in the control, we hypothesized that it plays a protective role during inflammation. This study provides a basis for further investigation of the expression and physiological role of Reg proteins in other mammals and broadens our understanding of the divergence and evolutionary conservation of Reg proteins in various mammalian species.