As a transgenic type 1 diabetic model, OVE26 mice develop diabetic nephropathy (DN) with the feature close to advanced DN in human, which makes it a valuable rodent model to study DN. Nevertheless, sexual differences in renal lesions, especially dynamic progression with different ages, remain undefined in OVE26 mice. To explore these issues, male and female OVE26 and wild type nondiabetic FVB mice at 4-, 12-, 24 - and 36-weeks old were used (N=6). Urine albumin-to-creatinine ratio (UACR) was detected to evaluate renal function. Renal histopathology and immunochemical and Western blotting protein expression of inflammation, tubular epithelial-myofibroblast transdifferentiation and fibrosis markers were examined. In FVB mice, blood glucose, triglyceride, UACR and podocytes numbers were constant during aging and comparable in male and female. Age-dependent slightly increase of glomerular mesangial matrix, inflammatory cells infiltration and renal fibrosis were observed in FVB mice. Compared with the age- and sex- matched FVB mice, male OVE26 mice developed hyperglycemia, mesangial matrix accumulation and increased trend of triglyceride at 4-week-old and albuminuria, glomerular enlargement, and upregulations of TGF-β1, α-SMA at 12 weeks old. Significant loss of podocytes, tubular dilation, collagen accumulation, increased trend of macrophage and T lymphocytes infiltrations, and increased protein levels of TNF-α, ICAM and fibronectin in kidney were observed in 24-week old male OVE26 mice. Compared with age-matched male OVE26 mice, female OVE26 mice had significant hypertriglyceridemia, worse renal function and kidney lesions at older age, including higher UACR and sustained loss of podocytes at age of 24 weeks; more inflammatory cells infiltration and renal fibrosis at age of 36 weeks. Our findings suggest the sexual difference in the progression of DN in OVE26 mice to provide evidence for researchers to properly select the age and sex of OVE26 mice in the future type 1 DN study.


W. Wang: None. L. Cai: None.

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