Khanna Ashwani, Plummer Matthew, Bromberek Cathy, Bresnahan Barbara, Hariharan Sundaram
Department of Medicine, Division of Nephrology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Kidney Int. 2002 Dec;62(6):2257-63. doi: 10.1046/j.1523-1755.2002.00668.x.
Long-term treatment with cyclosporine (CsA) or tacrolimus (Tac) results in chronic nephrotoxicity. Transforming growth factor-beta (TGF-beta) and other pro-fibrogenic molecules have been known to contribute to this side effect. A comparison of intrarenal expression of TGF-beta and other fibrogenic genes in biopsies from patients with either CsA or Tac nephrotoxicity have not been documented. This study compared the expression of TGF-beta, collagen, fibronectin, metalloproteinases (MMP-2, -9), tissue inhibitors of metalloproteinases (TIMP-2) and osteopontin in renal biopsies obtained from renal transplant recipients treated with either CsA or Tac as primary immunosuppressive agents.
Using RT-PCR, intrarenal expression of TGF-beta, collagen, fibronectin, MMP-2, MMP-9 and TIMP-2 were studied in renal biopsies from patients with histological diagnosis of CsA or Tac nephrotoxicity and acute rejection. TGF-beta protein expression was studied by staining section of biopsies with anti-TGF-beta antibody.
Intrarenal expression of TGF-beta, collagen, fibronectin, MMP-2, TIMP-2, and osteopontin were significantly increased in patients treated with Tac nephrotoxicity compared with CsA nephrotoxicity. The intrarenal mRNA expression of these genes was higher in patients diagnosed with Tac/CsA nephrotoxicity compared to acute rejection.
This study compares the intrarenal expression of TGF-beta and profibrogenic genes in renal transplant recipients treated with Tac and CsA. The results show that patients diagnosed with Tac nephrotoxicity exhibit increased expression of profibrogenic genes compared to CsA nephrotoxicity.
长期使用环孢素（CsA）或他克莫司（Tac）进行治疗会导致慢性肾毒性。已知转化生长因子-β（TGF-β）和其他促纤维化分子会导致这种副作用。CsA或Tac肾毒性患者活检组织中TGF-β和其他纤维化基因的肾内表达比较尚未见报道。本研究比较了以CsA或Tac作为主要免疫抑制剂治疗的肾移植受者肾活检组织中TGF-β、胶原蛋白、纤连蛋白、金属蛋白酶（MMP-2、-9）、金属蛋白酶组织抑制剂（TIMP-2）和骨桥蛋白的表达。
采用逆转录聚合酶链反应（RT-PCR），研究CsA或Tac肾毒性及急性排斥反应组织学诊断患者肾活检组织中TGF-β、胶原蛋白、纤连蛋白、MMP-2、MMP-9和TIMP-2的肾内表达。用抗TGF-β抗体对活检组织切片进行染色，研究TGF-β蛋白表达。
与CsA肾毒性患者相比，Tac肾毒性患者肾内TGF-β、胶原蛋白、纤连蛋白、MMP-2、TIMP-2和骨桥蛋白的表达显著增加。与急性排斥反应相比，诊断为Tac/CsA肾毒性患者这些基因的肾内mRNA表达更高。
本研究比较了Tac和CsA治疗的肾移植受者肾内TGF-β和促纤维化基因的表达。结果表明，与CsA肾毒性相比，诊断为Tac肾毒性的患者促纤维化基因表达增加。
