Department of Nephrology, The Third Affiliated Hospital of Southern Medical University, China.
Department of Nephrology, The Third Affiliated Hospital of Southern Medical University, China.
Transpl Immunol. 2019 Jun;54:20-28. doi: 10.1016/j.trim.2019.01.002. Epub 2019 Jan 22.
Chronic renal allograft dysfunction (CRAD) is the main condition affecting the long-term survival of renal allografts. Rosiglitazone, which is a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, has been shown to exert antifibrotic and anti-inflammatory effects on some renal diseases. The present paper investigates the effect of rosiglitazone on CRAD using a murine model.
The CRAD group received classical orthotopic F344-Lewis kidney transplantation. The treatment group was treated with rosiglitazone for 12 weeks following renal transplantation. The control subjects were uninephrectomized F344 and Lewis rats. Twelve weeks after the operation, the rats were harvested for renal function, histological, immunohistochemical and molecular biological analyses.
Rosiglitazone treatment effectively decreased urine protein excretion and preserved renal function in the CRAD rats. Administration of rosiglitazone also inhibited interstitial fibrosis and macrophage infiltration in the CRAD rat kidneys. Furthermore, rosiglitazone treatment inhibited TGF-β and NF-κB pathway activation, decreased collagen I, collagen IV, α-SMA, MCP-1, ICAM-1, TNF-α, and IL-1β expression, and increased E-cadherin expression in renal allograft tissues from the CRAD rats.
Rosiglitazone successfully attenuates the development of CRAD via inhibition of TGF-β signaling, the renal tubular epithelial-to-mesenchymal transition (EMT), and inflammation.
慢性移植肾失功（CRAD）是影响肾移植长期存活的主要因素。罗格列酮是过氧化物酶体增殖物激活受体-γ（PPAR-γ）激动剂，已被证明对某些肾脏疾病具有抗纤维化和抗炎作用。本研究采用小鼠模型探讨罗格列酮对 CRAD 的作用。
CRAD 组接受经典同基因 F344-刘易斯肾移植。移植后 12 周，治疗组给予罗格列酮治疗。对照组为单侧肾切除的 F344 和 Lewis 大鼠。术后 12 周，收获大鼠进行肾功能、组织学、免疫组织化学和分子生物学分析。
罗格列酮治疗可有效减少 CRAD 大鼠的尿蛋白排泄，保护肾功能。罗格列酮还可抑制 CRAD 大鼠肾脏间质纤维化和巨噬细胞浸润。此外，罗格列酮可抑制 TGF-β和 NF-κB 通路的激活，减少胶原 I、胶原 IV、α-SMA、MCP-1、ICAM-1、TNF-α和 IL-1β的表达，增加 CRAD 大鼠肾移植组织中 E-钙黏蛋白的表达。
罗格列酮通过抑制 TGF-β信号、肾小管上皮间质转化（EMT）和炎症成功减轻 CRAD 的发展。
