[The effects of mycophenolate mofetil on renal interstitial fibrosis and epithelial-myofibroblast translation in adenine-induced renal failure rats].

Abstract

OBJECTIVE:

The aim of this study is to examine the effect of mycophenolate mofetil (MMF) on epithelial-myofibroblast translation (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 creatinine levels were measured, and the histopathologic degrees of interstitial fibrosis were evaluated in Masson-stained sections. Expressions of alpha-smooth muscle actin (alpha-SMA), transforming growth factor beta1 (TGFbeta1), 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 alpha-SMA in MMF group was lower than that in CRF rats at week 6, 8 (P < 0.01), while expression of TGFbeta1 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 TGFbeta1 in renal tissue. The exact mechanism needs to be studied further.

• Authors: Chun-mei He, Fa-lei Zheng, Yan-ping Liu
• Journal: Zhonghua nei ke za zhi (Zhonghua Nei Ke Za Zhi) Vol. 47 Issue 11 Pg. 901-5 (Nov 2008) ISSN: 0578-1426 [Print] China
• PMID: 19080229 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Transforming Growth Factor beta
• Vascular Endothelial Growth Factor A
• Mycophenolic Acid

Topics

• Animals
• Kidney (drug effects, metabolism, pathology)
• Kidney Failure, Chronic (metabolism, pathology)
• Kidney Tubules (metabolism, pathology)
• Male
• Mycophenolic Acid (analogs & derivatives, pharmacology)
• Rats
• Rats, Wistar
• Transforming Growth Factor beta (metabolism)
• Vascular Endothelial Growth Factor A (metabolism)