title: Mycophenolate mofetil inhibits macrophage infiltration and kidney fibrosis in long-term ischemia-reperfusion injury.
abstract: Immunosuppressants have been widely used in renal transplantation, in which ischemia-reperfusion injury is inevitable. Mycophenolate mofetil (MMF) is a relative novel immunosuppressant and also attenuates ischemia-reperfusion injury in the acute phase, but its long-term effects are still obscure. Unilateral renal ischemia-reperfusion injury model was established in Sprague-Dawley rats and 30 mg/kg/day MMF or natural saline was administered a day before the surgery. Renal function was monitored, and histological changes and fibrosis in the kidney were evaluated in both short and long terms. TGF-β1 secretion and MCP-1 expression were determined by immunohistochemistry and real-time PCR respectively. The infiltration of macrophages in renal tissues was also assessed by fluorescence activated cell sorting (FACS). MMF treatment significantly improved renal function in ischemia-reperfusion injury rats in the short and long-term and also effectively prevented interstitial fibrosis. TGF-β1 secretion and MCP-1 expression in the renal tissue of MMF-treated rats were much lower than those in natural saline-treated rats, with much less macrophage infiltration as well. MMF treatment effectively prevented the deterioration of renal function and interstitial fibrosis in ischemia-reperfusion injury rats, which may be associated with decreased TGF-β1, MCP-1 and macrophages. These results provide evidence for the choice of MMF in the renal transplant patients not only for acute renal injury but also for long-term survival of renal allograft.
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai 200032, PR China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Jiang
authors.forename: Qunye
authors.initials: Q
authors.lastname: Tang
authors.forename: Ruiming
authors.initials: R
authors.lastname: Rong
authors.forename: Liangfeng
authors.initials: L
authors.lastname: Tang
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.forename: Jidong
authors.initials: J
authors.lastname: Lu
authors.forename: Yichen
authors.initials: Y
authors.lastname: Jia
authors.forename: Yitreen
authors.initials: Y
authors.lastname: Ooi
authors.forename: Jun
authors.initials: J
authors.lastname: Hou
authors.forename: Jianming
authors.initials: J
authors.lastname: Guo
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.forename: Tongyu
authors.initials: T
authors.lastname: Zhu
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005355:Fibrosis; D005786:Gene Expression Regulation / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology*; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000276:immunology* / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D007166:Immunosuppressive Agents; D053773:Transforming Growth Factor beta1; D009173:Mycophenolic Acid