Coordinated induction of VEGF receptors in mesenchymal cell types during rat hepatic wound healing (original) (raw)
- Original Paper
- Published: 14 July 1998
- M Matli1,
- K B Chang1,
- A Lalazar1,
- D B Donner2,
- L Wong1,
- R S Warren1 &
- …
- S L Friedman1
Oncogene volume 17, pages 115–121 (1998)Cite this article
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Abstract
Homology PCR has been used to identify receptor tyrosine kinases (RTKs) expressed during activation of rat hepatic stellate cells, the key fibrogenic mesenchymal element in the liver. Partial cDNAs encoding several RTKs were cloned from stellate cells activated in vivo, including those of Flt-1, Flk-1, c-met, PDGFR, and Tyro10/DDR2. RNAse protection from cells activated in vivo demonstrated biphasic induction of flt-1 and flk-1 mRNAs, receptors for vascular endothelial growth factor (VEGF). Culture-activation of stellate cells was associated with increased [125I]VEGF binding and Flt-1 and Flk-1 receptor protein. Induction of VEGF binding sites correlated with an 2.5-fold increase in DNA synthesis in response to VEGF, but only if cells were activated by growth on collagen I, whereas cells maintained in a quiescent state on a basement membrane-like substratum (EHS matrix) were nonproliferative. In both stellate and endothelial cells VEGF-induced mitogenesis was augmented by co-incubation with basic fibroblast growth factor (bFGF), a cytokine with known synergy with VEGF. These findings suggest that the cellular targets of VEGF in liver may not be confined to sinusoidal endothelial cells, and that VEGF responses reflect combined effects on both hepatic stellate cells and sinusoidal endothelium.
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Author notes
- V Ankoma-Sey
Present address: Division of Gastroenterology, University of Texas at Houston Medical School, 6431 Fannin, MSB 4.23, Houston, 77030, Texas, USA
Authors and Affiliations
- UCSF Liver Center & Departments of Medicine & Surgery, University of California, San Francisco, California, USA
V Ankoma-Sey, M Matli, K B Chang, A Lalazar, L Wong, R S Warren & S L Friedman - Department of Physiology and Biophysics and the Walther Oncology Center, University of Indiana, Indiapolis, Indiana, USA
D B Donner
Authors
- V Ankoma-Sey
- M Matli
- K B Chang
- A Lalazar
- D B Donner
- L Wong
- R S Warren
- S L Friedman
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Ankoma-Sey, V., Matli, M., Chang, K. et al. Coordinated induction of VEGF receptors in mesenchymal cell types during rat hepatic wound healing.Oncogene 17, 115–121 (1998). https://doi.org/10.1038/sj.onc.1201912
- Received: 07 October 1997
- Revised: 17 February 1998
- Accepted: 18 February 1998
- Published: 14 July 1998
- Issue date: 09 July 1998
- DOI: https://doi.org/10.1038/sj.onc.1201912