| 18929863 |
Song J, Lu YP, Luo GH, Yang L, Ma X, Xia QJ, Shi YJ, Li YP: Effects of mycophenolate mofetil on chronic allograft nephropathy by affecting RHO/ROCK signal pathways. Eur J Clin Invest. 2008 Jun;38(6):410-20.
AIM: We sought to investigate the effects of mycophenolate mofetil (MMF) on chronic allograft nephropathy (CAN) by affecting Rho and ROCK signal pathways. METHODS: Male inbred F344 rat renal grafts orthotopically transplanted into Lewis rats were first treated with CsA (10 mg/kg (-1).d (-1) x 10 d) and then divided into 3 groups (each n = 9): (1) orally vehicle, (2) cyclosporine (CsA, 6 mg/kg (-1).d (-1)) and (3) MMF (20 mg/kg (-1).d (-1)). In addition we performed autografts of F344 (n = 10) at 4, 8, and 12 weeks, serum creatinine (SCr) was measured and pathologic changes assessed. Expression of RhoA and ROCK-1 was determined by real-time reverse transcriptase polymerase chain reaction. Expressions of alpha-smooth muscle actin (alpha-SMA) and connective tissue growth factor (CTGF) were observed by immunohistochemistry. RESULTS: SCr and Banff score began to increase at 4 weeks in all 3 allografted groups with obvious deterioration in both the vehicle and CsA groups at 8 and 12 weeks. The differences between vehicle/CsA and autografts were significant (P = .000). SCr and Banff score among the MMF group increased mildly and moderately at 8 and 12 weeks, respectively, but were significantly lower than those in the vehicle/CsA cohort (P < .05). Expressions of RhoA and ROCK-1 mRNAs and proteins were observed in mesangial and tubular cells, increasing gradually along with the progression of chronic allograft nephropathy (CAN). There was a negative correlation between RhoA/ROCK-1 mRNA and Banff score (r = -.637, p = .000; r = -.676, P = .000) or SCr (r = -.705, P = .000; r = -.756, P = .000). MMF downregulated gene and protein expressions of RhoA and ROCK-1. CsA had little effect on these expressions. Expressions of alpha-SMA and CTGF were observed in renal epithelial and tubular cells. CONCLUSION: Herein we have demonstrated abnormal expression of RhoA and ROCK-1 signal pathways, which may play roles in CAN. MMF may attenuate CAN by downregulating the expression of RhoA/ROCK-1, alpha-SMA, and CTGF. |
3(0,0,0,3) |