Sirolimus toxicity and vascular endothelial growth factor release from islet and renal cell lines

被引：28

作者：

Laugharne, Matthew ^{[1
]}

Cross, Sarah ^{[1
]}

Richards, Sarah ^{[1
]}

Dawson, Charlotte ^{[1
]}

Ilchyshyn, Laura ^{[1
]}

Saleem, Moin ^{[1
]}

Mathieson, Peter ^{[1
]}

Smith, Richard ^{[1
]}

机构：

[1] Southmead Hosp, Paul Ogorman Lifeline Ctr, Clin Sci N Bristol, Acad Renal Unit, Bristol, Avon, England

来源：

TRANSPLANTATION | 2007年 / 83卷 / 12期

基金：

英国医学研究理事会;

关键词：

rapamycin; sirolimus; islet; podocyte; vascular endothelial growth factor (VEGF);

D O I：

10.1097/01.tp.0000266555.06635.bf

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Presently, sirolimus (rapamycin) is used as both induction and maintenance immunosuppression in solid organ transplants, including whole pancreas and kidney, and islet transplantation. Sirolimus has been suggested to have deleterious effects on islet beta-cell and renal function. We investigated the effect of sirolimus on the viability of islets, podocytes, and renal tubular cells. Sirolimus reduced the viability of islets and HK-2 human proximal renal tubular cells in vitro. This toxic effect was associated with a reduction of vascular endothelial growth factor (VEGF) release by islets but not the proximal tubular cells. Sirolimus reduced both viability and VEGF production by murine beta-cells, and blockade of VEGF-164 was associated with a reduction in viability. Transfection of murine islets with adenoviral VEGF-165 improved islet viability. These data are consistent with the hypothesis that sirolimus is toxic to islets and beta-cells by blockade of VEGF-mediated survival pathways.

引用

页码：1635 / 1638

页数：4

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