Effect of mycophenolate mofetil on the expression of p38 mitogen-activated protein kinase signal pathway in protein-overload rats

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SHUI Hua(Department of Nephrology, Zhongnan Hospital, Wuhan University, Wuhan 430071, China)
GAO Ping(Department of Nephrology, Zhongnan Hospital, Wuhan University, Wuhan 430071, China)
SI Xiao-yun(Department of Nephrology, Zhongnan Hospital, Wuhan University, Wuhan 430071, China)
Journal Title:
Volume 15, Issue 04, 2009
Key Word:
Mycophenolate mofetil;Mitogen-aetivated protein kinases;Nuclear factor kappa B;Nephrosis;Model;animal

Abstract: Objective To investigate the effect of mycophenolate mofetil (MMF) on the expression of p38 mitogen- activated protein kinase (MAPK) signal pathway in protein- overload nephrotic rats. Methods Thirty SD rats were divided into three groups (n=10 each): control group (normal saline), BSA group [protein-overload nephrotic rats, bovine serum albumin (BSA) group] and treatment group (BSA+ MMF). The protein-overload nephrotic rats were used. After 4 weeks, urinary proteins in 24 h, blood urea nitrogen (BUN) and serum creatinine were measured. Immunhistochemistry was applied to measure the expression of NF-κB. The activity of NF-κB was determined by electrophoretic mobility shift assay (EMSA). Western blot was performed to determine p38 MAPK protein. Renal tissues were examined by light microscopy and electron microscopy. Results The histological changes of BSA group showed tubular atrophy, widening of intertubular spaces with increased lymphocytes and mononuelear cells infiltration and fibrosis. Such histological changes were obriously improved in treatment group. Compared with the control group, urinary protein [(48.3±3.3) mg/24 h vs (67.8±4.5)mg/24 h, P<0.05], expression of NF-κB and p38 MAPK (45.24±6.25 vs 88.59±7.43; 80.68±8.34 vs 235.23±10.41) were significantly increased in protein-overload nephrotic rats (P<0.05). There were positive correlations of p38 MAPK with NF-κB and urinary protein (r=0.72, r=0.65, P<0.05). Compared with BSA group, MMF inhibited the expression of p38 MAPK, NF-κB and partly decreased the level of urinary protein [(59.1±4.2) mg/24 h,P<0.05]. Conclusion MMF can inhibit the expression of NF-κB and its mechanism may be due to the inhibition of p38 MAPK phosphorylation.

  • [1]费忠化,唐德粲.百令对慢性肾衰竭模型肾脏保护和肾结缔组织生长因子表达的影响.中华生物医学工程杂志,2008,14:105-109.
  • [2]Eddy AA,Kim H,Lopez-Guisa J,et al.Interstitial fibrosis in mice with overload proteinuria:deficiency of TIMP-1 is not protective.Kidney Int,2000,58:618-628.
  • [3]Nangaku M,Pippin J,Couser WG.C6 mediates chronic progression of tubulointerstitial damage in rats with remnant kidneys.J Am Soc Nephrol,2002,13:928-936.
  • [4]Tang S,Leung JC,Abe K,et al.Albumin stimulates interleukin-8 expression in proximal tubular epithelial cells in vitro and in vivo.J Clin Invest,2003,111:515-527.
  • [5]Rodriguez-Iturbe B,Ports H,Herrera-Acosta J,et al.Role of immunocompetent cells in nonimmune renal diseases.Kidney Int,2001,59:1626-1640.
  • [6]Ysehaert DK,De-Greef KE,Vercanteren SR,et al.Effect of immunosuppression on damage,leukocyte infiltration,and regeneration after severe warm ischemia/reperfusion renal injury.Kidney Int,2003,64:864-873.
  • [7]Donadelli R,Zanchi C,Morigi M,et al.Protein overload induces fractalkine upregulation in proximal tubular cells through nuclear factor kappaB and p38 mitogen-activated protein kinese-dnpendent pathways.J Am Soc Nephrol,2003,14:2436-2446.
  • [8]Morisi M,Macconi D,Zoja C,et al.Protein overload-induced NF-kappaB activation in proximal tubular cells requires H2O2 through a PKC-dependent pathway.J Am Soc Nephrol,2002,13:1179-1189.
  • [9]Takaya K,Koya D,Isono M,et al.Involvement of ERK pathway in albumin-induced MCP-1 expression in mouse proximal tubular cells.Am J Physiol Renal Physiol,2003,284:1037-1053.
  • [10]Stambe C,Atkins RC,Tesch GH.The role of p38 alpha mitogenactivated protein kinase activation in renal fibrosis.J Am Soc Nephrol,2004,15:370-379.
  • [11]张梅,唐嘉薇,李晓玫.p38丝裂素活化蛋白激酶信号转录对IL-1β诱导肾小管细胞转分化的影响.中华医学杂志,2003,83:1161-1165.
  • [12]Dai C,Yang J,Liu Y.Transforming growth factor-beta 1 potentiates renal tubular epithelial cell death by a mechanism independent of Smad signaling.J Biol Chem,2003,278:12537-12545.
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