Abstract: TH-PO690

FcgRIIb-Deficience and FcgRIII-Deficience Exacerbate Renal Injury Respectively in Diabetic Mice

Session Information

Category: Diabetes

  • 501 Diabetes Mellitus and Obesity: Basic - Experimental

Author

  • Zhang, Rui, Sichuan university, Chengdu, Sichuan province, China
Background

Fcg receptors are key immune receptors responsible for both humoral and innate immunity. FcgRI, FcgRIIb and FcgRIII are the members of Fcg receptors superfamily. We aimed to investigate the involvement of Fcg receptors respectively in diabetic mice.

Methods

Eight week-old C57BL/6 mice, FcgRIIb knockout mice and FcgRIII knockout mice were subdivided into three groups: the normal diet group, high fat diet group, type 2 diabetes group induced by high fat diet combined with streptozotocin. The levels of blood glucose, serum creatinine, urineprotein were tested. The expressions of TGF-β, TNF-α, pNK-κB, oxLDL were detected by real-time PCR or westernblot in isolated glomeruli. In vitro studies were performed in mice renal glomerular mesangial cell (GMCs) tranfected with lentivirus vectors carrying siRNA targeting FcgRIII, FcgRII and FcgRI gene respectively. GMCs were cultured with normal glucose, high glucose, oxLDL, high glucose combined with oxLDL.

Results

FcgRIII-/- diabetic mice and FcgRIIb-/- diabetic mice had elevated levels of fasting blood glucose, creatinine, urine protein compared with WT diabetic mice. Renal histology showed mesangial expansion, westernblot and real-time PCR indicated higher expression of TGF-β, TNF-α and pNK-κB, immunofluorescence or immunohistochemistry showed expressing in glomeruli, in diabetic FcgRIII knockout and FcgRIIb knockout than wild type and HFD respectively. The HFD group exist more severely biochemical dates, renal injury factors than control group and appeared most oxLDL deposition. To further examine the mechanism that which fc gamma receptor exacerbated renal injury for the most part, in vitro we observed that high glucose, high glucose combined with oxLDL activated expression of TGF-β, TNF-α, pNF-κB in mice renal glomerular mesangial cells, the transfection of FcgRIIb or FcgRIII siRNA had upregulated TGF-β, TNF-α, pNF-κB expression, whereas the transfection of FcgRI siRNA had appeared to attenuate the level of TGF-β,TNF-α, pNF-κB expression.

Conclusion

FcgRI deficience downregulated inflammation, fibrosis. FcgRIIb deficience accelarated inflammation, fibrosis and anomalous deposition of oxLDL. FcgRIII deficience failed to delay renal injury. These observations suggest that FcgRs represent a novel target in the therapeutic interventions for diabetic nephropathy.
Funding: The National Natural Science Foundation of China

Funding

  • Government Support - Non-U.S.