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.
My Menu
Saved Items

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 TGFβ-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 TGFβ-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



Export this article
Export this article as RIS | Text
 
Referenced by
6 newer articles

  1. Davani, Behrous (2009) Human islet-derived precursor cells can cycle between epithelial clusters and mesenchymal phenotypes. Journal of Cellular and Molecular Medicine 13(8b)
    [CrossRef]
  2. Johansson, Åsa (2009) Angiostatic factors normally restrict islet endothelial cell proliferation and migration: implications for islet transplantation. Transplant International
    [CrossRef]
  3. Smith, R Neal (2008) Pathology of an Islet Transplant 2 Years After Transplantation: Evidence for a Nonimmunological Loss. Transplantation 86(1)
    [CrossRef]
  4. Boonen, Kurt (2009) Bioactive peptides, networks and systems biology. BioEssays 31(3)
    [CrossRef]
  5. Laybutt, D. R. (2007) Influence of diabetes on the loss of beta cell differentiation after islet transplantation in rats. Diabetologia
    [CrossRef]
  6. Chu, Sheng-hua (2007) Hepatocyte growth factor production is stimulated by gangliosides and TGF-? isoforms in human glioma cells. Journal of Neuro-Oncology
    [CrossRef]
Remote Address: 38.107.191.101 • Server: mpweb06
HTTP User Agent: CCBot/1.0 (+http://www.commoncrawl.org/bot.html)