#4313 AN ANTI-FIBROTIC GENE ATTENUATES DIABETIC KIDNEY INJURY IN DB/DB MICE BY INHIBITING FIBROSIS VIA EPITHELIAL-MESENCHYMAL TRANSITION PATHWAY

Abstract

Abstract Background and Aims Diabetic nephropathy (DN) is a major cause of mortality in patients with diabetes and chronic kidney disease, but there is a lack of effective therapeutic drugs for this disease. The development and progression of DN is influenced by fibrosis. transforming growth factor (TGF)-β1 is a key cytokine involved in fibrosis in many different organ systems. Anti-fibrotic gene (Anti-F) is a TGF-β/Smad signaling. Here we examined the therapeutic effect of Anti-F in a model of DN using db/db mice with streptozotocin (STZ) treatment. Method The db/db mice were divided into five groups; db/m+ (wild type), db/db+saline, db/db+STZ, db/db+STZ+CMV-Anti-F, and db/db+STZ+TGF-β-Anti-F. STZ was peritoneally injected for five consecutive days (50mg/kg) and Anti-F (40μg/head) was peritoneally administered once every two weeks. Mice were sacrificed four months after STZ injection. Results The Anti-F with CMV and TGF-β promoter administration markedly alleviated metabolic syndrome assessed by obesity and hyperglycemia, and renal dysfunction assessed by renal overweight and albuminuria in db/db+STZ mice. The administration obviously mitigated glomerular damage in diabetic mice, as reflected by the reduction of increased mesangial expansion and the expression of nephrin and podocin in db/db+STZ mice. Additionally, renal interstitial fibrosis was also significantly inhibited by Anti-F through suppressing epithelial-mesenchymal transition (EMT) signaling including α-SMA, Twist, and Snail, as well as inflammation reflected by IL-1β, MMP-2, and MMP-9 in diabetic mice. Conclusion Anti-F attenuated the development of DN in db/db mice with type 2 diabetes. The protective effect was associated with decreased inflammation and subsequent attenuation of EMT-mediated renal fibrosis. Thus, this study suggests that targeting the Anti-F could be considered as a novel therapeutic approach for preventing the progression of DN.