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Differential regulation of VEGF by TGF-β and hypoxia in rat proximal tubular cells
- Title
- Differential regulation of VEGF by TGF-β and hypoxia in rat proximal tubular cells
- Authors
- Nakagawa T.; Lan H.Y.; Zhu H.J.; Kang D.-H.; Schreiner G.F.; Johnson R.J.
- Ewha Authors
- 강덕희
- SCOPUS Author ID
- 강덕희
![scopus](/images/layout/icon2.png)
- Issue Date
- 2004
- Journal Title
- American Journal of Physiology - Renal Physiology
- ISSN
- 0363-6127
- Citation
- American Journal of Physiology - Renal Physiology vol. 287, no. 4 56-4, pp. F658 - F664
- Indexed
- SCOPUS
![scopus](/images/layout/scopus2.gif)
- Document Type
- Article
- Abstract
- VEGF expression by proximal tubular epithelial cells may play a critical role in maintaining peritubular capillary endothelium in renal disease. Two major processes involved in renal injury include hypoxia (from vasoconstriction or vascular injury) and transforming growth factor (TGF)-β-dependent fibrosis, both of which are known to stimulate VEGF. Because the TGF-β/Smad pathway is activated in hypoxia, we tested the hypothesis that the induction of VEGF in hypoxia could be partially dependent on TGF-β. Rat proximal tubular (NRK52E) cells treated with TGF-β under normoxic conditions secreted VEGF at 24 h, and this was significantly reduced by blocking Smad activation by overexpressing the inhibitory Smad7 or by blocking p38 and ERK1/2 MAP kinase activation or protein kinase C activation with specific inhibitors. With acute hypoxia, rat proximal tubular cells also express VEGF mRNA and protein as well as TGF-β. However, the induction of VEGF occurs before synthesis of TGF-β and is not blocked by either a TGF-β antagonist, by Smad7 overexpression, or by blockage of ERK1/2, whereas induction is blocked by PKC inhibition or partially blocked by a p38 inhibitor. Finally, the addition of TGF-β with hypoxia results in significantly more VEGF expression than either stimulation alone. Thus TGF-β and hypoxia act via additive/synergistic but distinct pathways to stimulate VEGF in proximal tubular cells, a finding that may be important in understanding how VEGF is stimulated in renal disease.
- DOI
- 10.1152/ajprenal.00040.2004
- Appears in Collections:
- 의과대학 > 의학과 > Journal papers
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