Welcome!
To use the personalized features of this site, please log in or register.
If you have forgotten your username or password, we can help.
|
 |
Effects of diabetes and hypoxia on gene markers of angiogenesis (HGF, cMET, uPA and uPAR, TGF-
α
, TGF-
β
, bFGF and Vimentin) in cultured and transplanted rat islets
| |
|
Effects of diabetes and hypoxia on gene markers of angiogenesis (HGF, cMET, uPA and uPAR, TGF- α, TGF- β, bFGF and Vimentin) in cultured and transplanted rat islets
B. Vasir1, P. Reitz1, G. Xu1, A. Sharma1, S. Bonner-Weir1 and G. C. Weir1
| (1) |
Section on Islet Transplantation and Cell Biology, Research Division, Joslin Diabetes Center and Department of Medicine, Harvard
Medical School, Boston, Massachusetts, USA, US |
Abstract
Aims/hypothesis. The vascularisation of newly transplanted islets originates from the recipients. Because islets transplanted into a diabetic
do less well than those transplanted into a euglycaemic environment, we examined the hypothesis that gene expression of angiogenic
factors in grafts is delayed in diabetes. These factors include hepatocyte growth factor (HGF) and its receptor c-MET, and
urokinase plasminogen activator (uPA) and its receptor uPAR, basic fibroblast growth factor (bFGF), TGF-α and TGF β-1.¶ Methods. Isolated rat islets were studied in vitro under normoxic and hypoxic culture conditions and gene expression was determined
with semi-quantitative multiplex RT-PCR. We found that HGF but not c-MET expression was induced by hypoxia in vitro. Using
syngeneic Lewis rats, gene expression was also studied in grafts on days 1, 3, 5, 7 and 14 after transplantation.¶ Results. In grafts of normoglycaemic rats, HGF expression was enhanced on day 3 and maintained whereas expression of c-MET fell and
remained down until day 14. Expression of uPA was up at day 3 and remained high; expression of uPAR was also up at day 3 but
then fell to control levels at day 14. Expression of bFGF, TGF-α and TGF β-1 persisted throughout. Vimentin, a marker of fibroblasts, had increased expression at day 1 which was further enhanced in
subsequent days. In the grafts of diabetic recipients the expression of HGF, uPA and uPAR were delayed, being clearly expressed
at day 5 rather than day 3. Vimentin expression was similarly delayed.¶ Conclusion/interpretation. This apparent delay in angiogenesis provides a potential mechanism for the less favourable outcomes of islets transplanted
into diabetic recipients. [Diabetologia (2000) 43: 763–772]
Keywords Diabetes, islet transplantation, angiogenesis, hepatocyte growth factor and c-MET receptor and urokinase plasminogen
activator, bFGF, TGF-β, TGF-α.
Received: 11 January 2000 and in revised form: 24 February 2000
|
|
|
|
|
|