Expression and regulation of a novel identified TNFAIP8 family is associated with diabetic nephropathy

Tumor necrosis factor-α-inducible protein 8 (TNFAIP8) family are very recently identified proteins which share considerable sequence homology to regulate cellular and immune homeostasis. However, it is unknown whether TNFAIP8 family is expressed in the kidney and contributes to the regulation of renal functions. Therefore, the present study was designed to characterize the members of TNFAIP8 family in the kidney and to explore their possible roles in the development and progression of diabetic nephropathy. By RT-PCR and Western blot analyses, we found that all members of TNFAIP8 family were detected in the kidney. TNFAIP8 and TIPE2 expression was significantly increased in glomeruli from streptozotocin (STZ)-induced diabetic rats, and this upregulation was further confirmed in renal biopsies of diabetic patients. In in vitro study, TNFAIP8 was upregulated in response to high glucose in mesangial cells rather than podocytes. Moreover, a direct correlation was observed between expression of TNFAIP8 and mesangial cell proliferation and this regulation was associated with NADPH oxidase-mediated signaling pathway. However, we failed to observe the upregulation of TIPE2 in both mesangial cells and podocytes in response to high glucose. In conclusion, the present study addressed the role of TNFAIP8 family in diabetic nephropathy. These findings for the first time demonstrate that TNFAIP8 is one of critical components of a signal transduction pathway that links mesangial cell proliferation to diabetic renal injury.

Research Highlights
► Four members of TNFAIP8 family are expressed in the kidney.
► TNFAIP8 and TIPE2 expression is upregulated in diabetic nephropathy.
► TNFAIP8 plays a role in high glucose-induced mesangial cell proliferation.
► Regulation of TNFAIP8 expression is associated with NADPH oxidase activity.