Abstract:

Objective   To investigate the expression of Tribble3 in renal tissues of db/db mice at different stages and its relationship with renal fibrosis in diabetic nephropathy (DN). Methods  A total of 15 12-week-old male db/db mice and 15 age-matched control db/m mice were enrolled in the study. Random blood glucose and body weight were detected weekly. Animals were divided into 3 groups and sacrificed at 16wk, 20wk and 25wk  respectively. The weight of body (WB), 24h urinary albumin excretion (UAE), serum creatinine (Scr) and blood urea nitrogen (BUN) were detected before death. Renal tissue was harvested for histologic staining to evaluate the morphologic change, and immunohistochemical staining to detect the expression of TRB3. Real time-PCR and Western blotting were used to quantify the TRB3 and TGF-β1 expression at mRNA and protein levels respectively. Results  Levels of UAE, Scr and BUN of db/db mice were higher than those of the controls (P<0.05, P<0.01). The relative area of mesangium matrix and the content of collage in db/db mice were increased significantly from 20wk compared with those of the controls (P<0.01). The relative area of interstitial fibrous tissue was statistically different at 16wk, 20wk, and 25wk (P<0.01). Expression of TRB3 and TGF-β1 in renal tissue of db/db mice increased from 20wk and showed significant difference between the two groups at 25wk. The expression of TRB3 was positively correlated with TGF-β1 protein (r=0.944, P<0.01) and renal interstitial fibrosis (r=0.857, P<0.05) in the DN group. Conclusion  Compared with the age-matched db/m mice, TRB3 expression increases significantly in the kidney of db/db mice and has positive correlation with renal fibrosis induced by DN.

Key words: Tribble3, Fibrosis, Diabetic nephropathy, Db/db mice, Transforming growth factor-β1