The role of IFI35 in lupus nephritis and related mechanisms

Abstract

Objectives: It’s reported that multiple genes in the IFN-γ/STAT1 pathway were hypomethylated and associated with the pathogenesis of lupus nephritis (LN). Our previous study using microarray analysis suggested that interferon induced 35-kDa protein (IFI35) was hypomethylated and increased in LN. However, the role of IFI35 in LN and related mechanism remains to be elucidate.

Methods: The expressions of IFNγR, STAT1, IFI35 and MBD2 in the human kidneys tissues was detected by real-time PCR and Western blot. The protein levels of IFI35 in the human kidney tissues were detected by immunohistochemistry. The methylation status of IFNγR, STAT1 and IFI35 were detected by methylation specific PCR. Cell proliferation assay was evaluated using cell counting kit 8; pcDNA-IFI35 (pcDNA-MBD2) or IFI35 RNAi (MBD2 RNAi) was used to upregulated or downregulated the expression of the IFI35 and MBD2.

Results: The expressions of IFNγR, STAT1 and IFI35 in the LN kidneys were significantly higher than controls. IFI35 was expressed in mesangial cells, and positively correlated with the proliferation of mesangial cells. IFNγR, STAT1and IFI35 was hypomethylated and MBD2 was increased in LN kidneys. In vitro data confirmed those findings: after stimulating with the serum from LN patients, the proliferation of human renal mesangial cells (HRMCs) was increased. The expressions of the three members of IFNγ signal pathway were hypomethylated and upregulated. However, this effect was reversed by MBD2 knockdown. IFI35 promoted the proliferation of HRMCs and was regulated by MBD2.

Conclusion: Our results demonstrated that IFI35 enhances the proliferation of mesangial cells and was regulated by MBD2 in LN.

Keywords:

• IFI35
• MBD2
• Hypomethylation
• Mesangial cells

Conflict of interest

None.

Additional information

Funding

This work was supported by grants from National Natural Science Foundation of China [81373206, 81401357], National High Technology Research and Development Program of China [2012AA02A513], Hunan Provincial Natural Science Foundation of China [13JJ5010] and Hunan Special Fund for Science and Technology Development Program [2013WK3022].