Abstract: FR-PO623

Investigation of Protein Tyrosine Phosphatase, Non-Receptor Type 2 (PTPN2) and Its Interaction with Vitamin D Receptor (VDR) in Inflammation of Type 2 Diabetes Mellitus

Session Information

Category: Diabetes

  • 501 Diabetes Mellitus and Obesity: Basic - Experimental

Authors

  • Zheng, Li, The Third Xiangya Hospital of Central South University, Changsha, China
  • Zhang, Wei, The Third Xiangya Hospital of Central South University, Changsha, China
  • Zhang, Hao, The Third Xiangya Hospital of Central South University, Changsha, China
Background

To investigate the role of protein tyrosine phosphatase nonreceptor type 2 (PTPN2) in the inflammation of type 2 diabetes mellitus (T2DM) and its interaction with vitamin D receptor(VDR).

Methods

101 T2DM patients were divided into three groups based on urinary albumin-to-creatinine ratio (uACR):normal albuminuria(30mg/g>uACR,n=29), microalbuminuria(30mg/g≤uACR<300mg/g,n=34),and macroalbuminuria(uACR≥300mg/g,n=38),with healthy individuals(n=18) as controls.Serum from these objects were analyzed for PTPN2 protein. Peripheral blood mononuclear cells (PBMCs) were cultured ex vivo to analyzed for PTPN2 and VDR in both protein and mRNA level.HK2 and THP1 cell were stimulated with tumor necrosis factor (TNF) or high glucose and treatment with paricalcitol. The expression of PTPN2 and VDR was analyzed by real-time PCR and Western blotting. The release of IL-6 and MCP-1 were analyzed by real-time PCR and ELISA after PTPN2 silencing or overexpression.

Results

PTPN2 expression was down-regulated in serum and PBMCs from T2DM patients with albuminuria and same with VDR expression in PBMCs.PTPN2 levels were negatively correlated with uACR. Logistic regression analysis revealed that PTPN2 down-regulation was an independent risk factor for the increase in uACR;PTPN2 expression was positively correlated with VDR expression in the PBMCs from T2DM patients.Stimulation of TNF-α or high glucose could both decrease the expression of PTPN2 and VDR in both protein and mRNA level in cultured HK2 and THP-1 cell,while treatment with paricalcitol can reverse the down-regulation of PTPN2 as well as VDR.After PTPN2 silencing in HK2 and THP-1 cell can significantly increased the production of the inflammatory cytokine IL-6 and chemokines MCP-1. Moreover, high PTPN2 levels contributed to decline the elevated IL-6and MCP-1.But treatment with paricalcitol after PTPN2 silencing could not reverse the up-regulation of IL-6 and MCP-1.

Conclusion

Down-regulation of serum PTPN2 is independently with the severity of albuminuria in T2DM.PTPN2 has anti-inflammatory activities in T2DM and the inflammation regulatory role may be associated with the Vitamin D/VDR pathway.