Expression of the Integrin-Linked Kinase in a Rat Kidney Model of Chronic Allograft Nephropathy
- 213 Downloads
The purpose of this study was to investigate the expression and significance of integrin-linked kinase (ILK) in the pathogenesis of chronic allograft nephropathy (CAN) in rats. For this, kidneys of Fisher (F344) rats were orthotopically transplanted into Lewis (LEW) rats. The animals were evaluated at 4, 8, 12, 16, and 24 weeks post-transplantation for renal function and histopathology. ILK protein expression was determined by Western-blot and immunohistological assays, and mRNA by RT-PCR. Our data show that 24-h urinary protein excretion in CAN rats increased significantly at week 16 as compared with F344/LEW controls. Allografts showed markedly increased mononuclear cells infiltration and presented with severe interstitial fibrosis and tubular atrophy at 16 and 24 weeks. ILK expression (protein/mRNA) was upregulated in rat kidneys with CAN, and the increase became more significant over time after transplantation. ILK expression correlated significantly with 24-h urinary protein excretion, serum creatinine levels, tubulointerstitial mononuclear cells infiltration, smooth muscle cells (SMCs) migration in vascular wall, and interstitial fibrosis. Therefore, it was concluded that ILK overexpression was the key event that involved mononuclear cells infiltration and vascular SMCs migration at early stage, and interstitial fibrosis and allograft nephroangiosclerosis at later stage of CAN pathogenesis in rats.
KeywordsIntegrin-linked kinase Chronic allograft nephropathy Interstitial fibrosis Vascular smooth muscle cells Nephroangiosclerosis
The authors thank Xiongfei Gu for excellent technical support. This study was funded by Xiamen Research Grant.
- 3.Scholten, E. M., Rowshani, A. T., Cremers, S., Bemelman, F. J., Eikmans, M., van Kan, E., et al. (2006). Untreated rejection in 6-month protocol biopsies is not associated with fibrosis in serial biopsies or with loss of graft function. Journal of the American Society of Nephrology, 17, 2622–2632.PubMedCrossRefGoogle Scholar
- 15.Sabattini, E., Bisgaard, K., Ascani, S., Poggi, S., Piccioli, M., Ceccarelli, C., et al. (1998). The EnVision++ system: A new immunohistochemical method for diagnostics and research. Critical comparison with the APAAP, ChemMate, CSA, LABC, and SABC techniques. Journal of Clinical Pathology, 51, 506–511.PubMedCrossRefGoogle Scholar
- 25.Shimizu, M., Kondo, S., Urushihara, M., Takamatsu, M., Kanemoto, K., Nagata, M., et al. (2006). Role of integrin-linked kinase in epithelial–mesenchymal transition in crescent formation of experimental glomerulonephritis. Nephrology, Dialysis, Transplantation, 21, 2380–2390.PubMedCrossRefGoogle Scholar