Increased Expression of p-Akt correlates with Chronic Allograft Nephropathy in a Rat Kidney Model.
Chronic allograft nephropathy (CAN) is the most common cause of chronic graft dysfunction leading to graft failure, our study investigates the expression and significance of p-Akt in the pathogenesis of CAN in rats. 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. Phosphorate Akt (p-Akt) protein expression was determined by Western blot and immunohistological assays. Our data show that 24-h urinary protein excretion in CAN rats increased significantly at week 16 as compared with F344/LEW controls. Allografts got severe interstitial infiltration of mononuclear cells at week 4 and week 8, but it was degraded as the time went on after week 16. Allografts markedly presented with severe interstitial fibrosis (IF) and tubular atrophy at 16 and 24 weeks. p-Akt expression was upregulated in rat kidneys with CAN, and the increase became more significant over time after transplantation. p-Akt 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 IF. It was concluded that p-Akt overexpression might be the key event that involved mononuclear cells infiltration and vascular SMCs migration at early stage, and IF and allograft nephroangiosclerosis at the late stage of CAN pathogenesis in rats.
Department of Nephrology, The No. 2 Hospital of Xiamen, Xiamen, 361021, China.
Li-Na
LN
Zhou
Medical College Xiamen University, Xiamen, China.
Ning
N
Wang
Department of Urology, The Affiliated School of Clinical Medicine, Xuzhou Medical College, 199 Jie Fang Nan Road, Xuzhou, 221009, China.
Yang
Y
Dong
Department of Nephrology, The No. 2 Hospital of Xiamen, Xiamen, 361021, China.
Yiqin
Y
Zhang
Department of Nephrology, The No. 3 Affiliated Hospital of Southern Medical University, Guanghzou, China.
Hequn
H
Zou
Department of Nephrology, The No. 2 Hospital of Xiamen, Xiamen, 361021, China.
Qingqin
Q
Li
Department of Nephrology, The No. 1 Affiliated Hospital of Wenzhou Medical College, Wenzhou, China.
Yangling
Y
Shi
Department of Nephrology, The No. 5 Affiliated Hospital of Sun Yat-sen University, Guanghzou, China.
Ling
L
Chen
Department of Nephrology, The No. 5 Affiliated Hospital of Sun Yat-sen University, Guanghzou, China.
Wenying
W
Zhou
Department of Urology, The Affiliated School of Clinical Medicine, Xuzhou Medical College, 199 Jie Fang Nan Road, Xuzhou, 221009, China. dyamler@gmail.com.
Conghui
C
Han
Department of Nephrology, The No. 2 Hospital of Xiamen, Xiamen, 361021, China. wyx1000@126.com.
Yuxin
Y
Wang
D064591:Allografts; D000818:Animals; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic; D007674:Kidney Diseases / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D010750:Phosphoproteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats
D010750:Phosphoproteins; D051057:Proto-Oncogene Proteins c-akt
Chronic allograft nephropathy; Kidney diseases; Kidney transplantation; p-Akt