Protective effect of rosiglitazone on chronic renal allograft dysfunction in rats

• Published in: Transplant immunology 2019-06, Vol.54, p.20-28
• Main Authors: Deng, Jin, Xia, Yue, Zhou, Qin, Wang, Xin, Xiong, Chongxiang, Shao, Xiaofei, Shao, Mengjiao, Zou, Hequn
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Chronic Disease; Chronic renal allograft dysfunction; Disease Models, Animal; Epithelial-Mesenchymal Transition - drug effects; Epithelial-to-mesenchymal transition; Fibrosis; Graft Rejection - drug therapy; Humans; Inflammation; Interstitial fibrosis; Kidney - metabolism; Kidney - pathology; Kidney Transplantation; Macrophages - immunology; Male; PPAR gamma - agonists; Rats; Rats, Inbred Lew; Rosiglitazone; Rosiglitazone - pharmacology; Rosiglitazone - therapeutic use; Signal Transduction - drug effects; Transforming Growth Factor beta - metabolism
• ISSN: 0966-3274; 1878-5492
• DOI: 10.1016/j.trim.2019.01.002

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. •Rosiglitazone successfully attenuates the development of CRAD in rats.•Rosiglitazone inhibited TGF-β signaling, the renal tubular EMT, and inflammation.•Rosiglitazone may represent a novel therapeutic strategy for CRAD.