Tranilast Prevents the Progression of Experimental Diabetic Nephropathy through Suppression of Enhanced Extracellular Matrix Gene Expression

Abstract

The present study was performed to investigate the effects of the antiallergic drug tranilast on the development of diabetic nephropathy in streptozotocin (50 mg/kg)-induced diabetic spontaneously hypertensive rats (SHR). Diabetic SHR were given standard chow or chow containing tranilast at a dose of 1400 mg/kg for 24 weeks. The effects of tranilast on urinary albumin excretion, mesangial expansion, expression of transforming growth factor-␤ (TGF-␤) and type I collagen mRNAs, number of anionic sites on the glomerular basement membrane (GBM), and urinary TGF-␤ and 8-hydroxy-2Ј-deoxyguanosine (8-OHdG) excretion were assessed. Tranilast did not affect the blood glucose concentration or blood pressure in diabetic SHR. Urinary albumin excretion rate and creatinine clearance were markedly increased in diabetic SHR. Tranilast treatment decreased albuminuria and hyperfiltration. Tranilast inhibited the diabetes-induced expansion of mesangial and tuft areas, as well as the increase in urinary TGF-␤ and 8-OHdG excretion, loss of anionic sites of GBM, and overexpression of TGF-␤ as determined immunohistochemically. The levels of TGF-␤ and type I collagen mRNA expression were increased in the renal cortex in untreated diabetic SHR at 24 weeks, as determined by real-time quantitative polymerase chain reaction. Tranilast treatment inhibited the up-regulation of TGF-␤ and type I collagen mRNA expression by 65 and 36%, respectively, in diabetic SHR. In conclusion, tranilast decreased albuminuria by suppressing glomerular hyperfiltration, mesangial expansion, and loss of the charge barrier via regulation of extracellular matrix gene expression and oxidative stress. Tranilast may be clinically useful in the treatment of diabetic nephropathy.

Reduction of Post-Surgical Adhesion Formation with Tranilast

“…In addition to its anti-proliferative effects, tranilast can inhibit various inflammatory responses [33][34][35], TGF-␤ production [26], and collagen production [36], all of which would be expected to negatively impact adhesion formation [37,38]. This same reduction in TGF-␤ and type 1 collagen was demonstrated in the kidneys of rats following streptozotocin induced diabetic nephropathy as well as in the heart of mRen-2 diabetic rats [39,40]. Tranilast dependent reduction in fibrosis was also found in mice FIG.…”

Bone Marrow-Derived Mononuclear Cells Promote Improvement in Glomerular Function in Rats with Early Diabetic Nephropathy

“…In the present diabetic nephropathy model, we were able to observe a reduction in TGF-β1 renal expression after treatment with bone marrow-derived MCs, along with a reduction in the glomerular filtration rate and glomerular tuff area to CTRL animal levels. The same observation was made in spontaneous hypertensive rats subjected to diabetes where the inhibition of TGF-β1 expression by tranilast, an antiallergic drug that inhibits the release of cytokines from macrophages and chemical mediators from mast cells [41], led to a reduction in glomerular hyperfiltration and glomerular tuff area expansion despite persistent hyperglycemia [42]. …”

Tranilast: A review of its therapeutic applications

“…This indicated that tranilast suppressed the accumulation of collagen in renal tissues and it may be a useful drug for diabetic nephropathy. In one survey, tranilast inhibited the diabetes-induced expansion of mesangial, decreased albuminuria by suppressing glomerular hyperfiltration, and it also suppressed the up-regulation of TGF-␤ and collagen expression in diabetic rats as well [147].…”