Research Article: Acute rejection after kidney transplantation promotes graft fibrosis with elevated adenosine level in rat

Date Published: June 26, 2017

Publisher: Public Library of Science

Author(s): Mingliang Li, Yingbo Dai, Jun Lei, Jin Tang, Yihong Zhou, Bing Xia, Yang Xia, Guangming Yin, Stanislaw Stepkowski.


Chronic allograft nephropathy is a worldwide issue with the major feature of progressive allograft fibrosis, eventually ending with graft loss. Adenosine has been demonstrated to play an important role in process of fibrosis. Our study aimed to investigate the relationship between adenosine and fibrosis in renal allograft acute rejection in rat.

Wistar rats and SD rats were selected as experimental animals. Our study designed two groups. In the allograft transplantation group, kidneys of Wistar rats were orthotopically transplanted into SD rat recipients, the same species but not genetically identical, to induce acute rejection. Kidney transplantations of SD rats to SD rats which were genetically identical were served as the control. We established rat models and detected a series of indicators. All data were analyzed statistically. P<0.05 was considered statistically significant. Compared with the control group, levels of adenosine increased significantly in the allograft transplantation group, in which acute rejection was induced (P<0.05). Progressive allograft fibrosis as well as collagen deposition were observed. These findings suggested that level of adenosine was upregulated in acute rejection after kidney allograft transplantation in rat. Acute rejection may promote renal allograft fibrosis via the adenosine signaling pathways.

Partial Text

Kidney transplantation is the most effective treatment of end-stage renal failure, however, incidence of chronic allograft nephropathy (CAN) remains high, which finally leads to renal allograft dysfunction. One of the major features seen in CAN is progressive allograft fibrosis. Hence, attention has been focused on pathogenesis of renal graft fibrosis to improve preventment and treatment of CAN.

This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Committee on the Ethics of the The Third Xiangya Hospital, Central South University. All surgery was performed under pentobarbital sodium anesthesia, and all efforts were made to minimize suffering.

A role of adenosine (ADO) in graft fibrosis was initially demonstrated by the striking graft fibrosis and dysfunction observed in renal acute rejection models, which are similar CAN. These findings demonstrated that adenosine may be an important fibrotic signaling molecule promoting graft fibrosis.




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