Effects of mycophenolic acid on high glucose-induced expression of TGF-β and CTGF in mesangial cells

Abstract

The effects of mycophenolic acid (MPA) on high glucose-induced expression of transforming growth factor-β (TGF-β) and connective tissue growth factor (CTGF) in mesangial cells (MC) were investigated. Rat MC were cultured in the presence of different concentrations of MPA (1.0 and 10.0 μmol/L) or MPA plus high glucose for 72 h. The expression of TGF-β and CTGF was detected by Western blot. The results showed that high glucose could induce the expression of TGF-β and CTGF in MC, but MPA could inhibit this effects. MPA did not influence the expression of TGF-β and CTGF in normal glucose. It was concluded that MPA might prevent the progression of diabetic nephropathy by inhibiting the expression of TGF-β and CTGF in MC.

Keywords

mycophenolic acid / transforming growth factor-β / connective tissue growth factor / mesangial cell / diabetic nephropathy

References

[1] UtimuraR, FujiharaC K, MattarA L, et al.. Mycophenolate mofetil prevents the development of glomerular injury in experimental diabetes. Kid Int, 2003, 63: 209-216

[2] YuT H, JiaR H, DingG H, et al.. Protective effects of mycophenolate mofetil on kidneys of type 2 diabetic rats. Chin J Clin Pharmacol Ther, 2004, 9(10): 1119-1122

[3] GrotendorstG R. Connective tissue growth factor: a mediator of TGF-β action on fibroblasts. Cytokine Growth Factor Rev, 1997, 8: 171-179

[4] GotendorstG R, OkochiH, HayashiN. A novel transforming growth factor-β response element controls the expression of the connective tissue growth factor gene. Cell Growth Differ, 1996, 7: 469-480

[5] IgarashiA, OkochiH, BradhamD M, GrotendorstG R. Regulation of connective tissue growth factor gene expression in human skin fibroblasts and during wound repair. Mol Biol Cell, 1993, 4: 637-645

[6] IgarashiA, NashiroK, KikuchiK, et al.. Significant correlation between connective tissue growth factor gene expression and skin sclerosis in tissue sections from patients with systemic sclerosis. J Invest Dermatol, 1995, 105: 280-284

[7] FrazierK S, WilliamsS, KothapalliD, et al.. Stimulation of fibroblast cell growth, matrix production and granulation tissue formation by connective tissue growth factor. J Invest Dermatol, 1996, 107: 404-411

[8] HayashidaT, SchnaperH W. High ambient glucose enhances sensitivity to TGF-beta1 via extracellular signal-regulated kinase and protein kinase Cdelta activities in human mesangial cells. J Am Soc Nephrol, 2004, 15(8): 2032-2041

[9] GarrettQ, KhawP T, BlalockT D, et al.. Involvement of CTGF in TGF-beta1-stimulation of myofibroblast differentiation and collagen matrix contraction in the presence of mechanical stress. Invest Ophthalmol Vis Sci, 2004, 45(4): 1109-1116

[10] HolmesA, AbrahamD J, SaS, et al.. CGTF and SMADs, maintenance of scleroderma phenotype is independent of SMAD signaling. J Biol Chem, 2001, 276(14): 10594-10601

[11] OemarB S, LuscherT F. Connective tissue growth factor, friend or foe?. Arterioscler Thromb Vasc Biol, 1997, 17(8): 1483-1489