Rapamycin inhibits transforming growth factor β-induced peritoneal angiogenesis by blocking the secondary hypoxic response.
Bottom Line: In primary mesothelial cell culture, rapamycin had no effect on TGFβ-induced vascular endothelial growth factor (VEGF) but did suppress hypoxia-induced VEGF.The fibrogenic effects of HIF1α were Smad3 dependent.The hypoxic response is mediated partly through HIF1α and the mTOR inhibitor rapamycin blocks the hypoxic-induced angiogenic effects but does not affect the direct TGFβ-mediated fibrosis and angiogenesis.
Affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada.Show MeSH
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Mentions: We studied induction of HIF1α after 24 hrs of exposure to recombinant TGFβ1. TGFβ1 did not significantly induce HIF1α protein or gene expression at this time point (Fig. 4A–C) and HIF1α protein and gene expression was not significantly affected by rapamycin. TGFβ1 significantly increased VEGF gene expression in mesothelial cell culture and rapamycin had no effect on this (Fig. 4D).
Affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada.