Protein Kinase D2 Protects against Acute Colitis Induced by Dextran Sulfate Sodium in Mice

Jing Xiong; Ming-Feng Zhou; Ya-Dong Wang; Li-Ping Chen; Wan-Fu Xu; Yao-Dong Wang; Fan Deng; Si-de Liu

doi:10.1038/srep34079

Protein Kinase D2 Protects against Acute Colitis Induced by Dextran Sulfate Sodium in Mice

Sci Rep. 2016 Sep 23:6:34079. doi: 10.1038/srep34079.

Authors

Jing Xiong¹, Ming-Feng Zhou^{1

2}, Ya-Dong Wang¹, Li-Ping Chen², Wan-Fu Xu², Yao-Dong Wang², Fan Deng², Si-de Liu¹

Affiliations

¹ Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
² Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.

Abstract

Inflammatory bowel disease is characterized by dysregulation of the mucosal immune system resulting from impaired intestinal epithelial barrier function. Protein kinase D2 has been implicated in the regulation of immune responses. The present study was to define PKD2 might affect murine colitis. Colitis was induced in wild-type mice (PKD2^WT/WT) and PKD2 catalytic activity deficient mice (PKD2^SSAA/SSAA) with dextran sulfate sodium. PKD2^SSAA-knockin mice displayed catalytic activity deficiency and increased susceptibility to DSS-induced colitis with enhanced weight loss, colonic inflammation compared with PKD2^WT/WT mice. Furthermore, crucial inflammatory cytokines mRNA levels in PKD2^SSAA-knockin mice were higher than controls accompanied with down-regulation of ZO-1, MUC2 and intestinal barrier dysfunction. However, there were no differences in the proliferation or apoptosis of intestinal epithelial cells in PKD2^SSAA-knockin mice compared with wild-type controls. In addition, PKD2 expression was repressed in patients with IBD compared with healthy controls. These studies suggested that activation of PKD2 in the colonic epithelium microenvironment may contribute to protect against DSS-induced colitis through regulation of intestinal mucosal immunity and barrier function.