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Overexpression of Suppressor of Cytokine Signaling 1 in Islet Graft results in Anti-Apoptosis Effect and Prolonged Survival
Qin Jie 1,Jiao Yang 2,Chen Xiaobo 2,Zhou Shuang 1,Liang Chunmin 1,Zhong Cuiping 1 *
1.Department of Anatomy, Histology and Embryology, Shanghai Medical College, Fudan University
2.Department of Urinary Surgery and Transplantation, Shanghai First People`s Hospital, Shanghai Jiaotong University
*Correspondence author
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Funding: 国家自然科学基金,教育部博士点基金,教育部博士点基金（No.No.30370748,No.20050246069,No.20070246051）
Opened online:13 January 2009
Accepted by: none
Citation: Qin Jie,Jiao Yang ,Chen Xiaobo .Overexpression of Suppressor of Cytokine Signaling 1 in Islet Graft results in Anti-Apoptosis Effect and Prolonged Survival[OL]. [13 January 2009] http://en.paper.edu.cn/en_releasepaper/content/27693
 
 
A significant portion of islet grafts are destroyed by apoptosis and fail to become functional after transplantation. Strategies which enhance islets’ anti-apoptosis ability may inhibit grafts loss. Aim of this study was to investigate whether overexpression of SOCS1 in islet grafts could achieve anti-apoptosis effect and prolonged grafts survival. We used chimeric adenovirus vector (Ad5F35) to enhance SOCS1 expression in isolated rat islets, and detected its protective action against rTNF-α induced apoptosis. After transplanting SOCS1-overexpressing islets into allogeneic recipients with streptozotocin-induced diabetes, grafts survival and in situ apoptosis were analyzed using immunohistochemistry. The isolated rat islets infected with Ad5F35 containing SOCS1 gene (Ad5F35-SOCS1, MOI=100) showed significantly higher SOCS1 expression than Ad5F35-EGFP and mock infected islets. After treatment with rTNF-α and cycloheximide for 48 hours in vitro, Ad5F35-SOCS1 infected islets exhibited lower apoptotic ratio (8.89±4.03%, P<0.05) than controls (Ad5F35-EGFP: 24.60±6.88%, mock infected: 21.14±5.12%). The diabetic recipients transplanted with Ad5F35-SOCS1 infected islets presented 12.14±2.12 days of normoglycemia, statistically longer than that of recipients transplanted with mock infected islets (6.20±1.48 days, P<0.05). Furthermore, histological analysis indicated that these infected grafts with local overexpression of SOCS1 had preserved islet function and suppressed cell apoptosis in the early posttransplant period. These results demonstrate that overexpression of SOCS1 in islet grafts prior to transplantation can significantly protect them from apoptosis loss and prolong their survival. This approach could be used to improve outcomes of islet transplantation in clinic.
Keywords:Diabetes;Islet transplantation;SOCS1;Apoptosis;Gene therapy
 
 
 

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