The effects of mycophenolate mofetil on renal interstitial fibrosis and epithelial-myofibroblast transiation in adenine-induced renal failure rats / 中华内科杂志

ABSTRACT

Objective The aim of this study is to examine the effect of myoophenolate mofetil (MMF) on epithelial-myofibroblast transiation(EMT) in adenine-induced chronic renal failure (CRF) rat model and the role of vascular endothelial growth factor(VEGF) and inhibitor of differentiation (Id2 and Id3) in EMT in the rat kidney. Methods Sixty-four male Wistar rats were randomly assigned to the following groups normal control (n=16), CRF (n=24) and MMF(n=24). CRF was induced by gastric gavage of adenine (125 mg·kg-1·d-1) to rats for eight weeks. CRF rats were treated with MMF (15 mg·kg-1·d-1) as "MMF" group. The rats were sacrificed at week 2, 4, 6 and 8, respectively.Urinary protein and serum ereatinine levels were measured, and the histopathologic degrees of interstitial fibrosis were evaluated in Massen-stained sections. Expressions of a-smooth muscle actin (α-SMA),transforming growth factor β1 (TGFβ1), VEGF and Id (Id2 and Id3) in the kidney tissue were assessed by immunohistochemistry, RT-PCR and/or Western blot methods. Results The urinary protein level in MMF group was evidently lower than that in CRF group (P<0.01), whereas no statistically significant difference was observed in serum creatinine level between the two groups. Renal interstitial fibrosis was reduced significantly with MMF treatment (P<0.01). Expression of α-SMA in MMF group was lower than that in CRF rats at week 6, 8 (P<0.01), while expression of TGFβ1 was decreased markedly at week 2, 4,6 (P<0.01). The expressions of VEGF in MMF rats were increased significantly at week 6,8 (P<0.01),and Id2,Id3 in MMF rats were increased significantly at week 4,6 (P<0.05). Conclusions MMF may ameliorate chronic renal fibrosis and EMT in adenine-induced CRF rats. This effect of MMF on EMT is probably related to upregulation of VEGF, Id2 and Id3 expressions and suppressing overexpression of TGFβ1 in renal tissue. The exact mechanism needs to be studied further.