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Intra- and extracellular signaling by endothelial neuregulin-1
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Iivanainen, Erika (author)
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Paatero, Ilkka (author)
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Heikkinen, Satu-Maria (author)
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Junttila, Teemu T. (author)
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- Cao, Renhai (author)
- Karolinska Institutet
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- Klint, Peter (author)
- Uppsala universitet,Institutionen för genetik och patologi
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Jaakkola, Panu M. (author)
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- Cao, Yihai (author)
- Karolinska Institutet
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Elenius, Klaus (author)
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(creator_code:org_t)
- Elsevier BV, 2007
- English.
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In: Experimental Cell Research. - : Elsevier BV. - 0014-4827 .- 1090-2422. ; 313:13, s. 2896-2909
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Suppression of tumor growth by inhibition of ErbB receptor signaling is well documented. However, relatively little is known about the ErbB signaling system in the regulation of angiogenesis, a process necessary for tumor growth. We have previously shown that heparin-binding EGF-like growth factor (HB-EGF) is expressed by vascular endothelial cells (EC) and promotes endothelial recruitment of vascular smooth muscle cells (SMC). To assess whether other members of the EGF-family regulate angiogenesis, the expression of 10 EGF-like growth factors in primary ECs and SMCs was analyzed. In addition to HB-EGF, neuregulin-1 (NRG-1) was expressed in ECs in vitro and in vivo. Endothelial NRG-1 was constitutively processed to soluble extracellular and intracellular signaling fragments, and its expression was induced by hypoxia. NRG-1 was angiogenic in vivo in mouse corneal pocket and chicken chorioallantoic membrane (CAM) assays. However, consistent with the lack of NRG-1 receptors in several primary EC lines, NRG-1 did not directly stimulate cellular responses in cultured ECs. In contrast, NRG-1 promoted EC responses in vitro and angiogenesis in CAM in vivo by mechanisms dependent on VEGF-A and VEGFR-2. These results indicate that NRG-1 is expressed by ECs and regulates angiogenesis by mechanisms involving paracrine up-regulation of VEGF-A.
Keyword
- endothelial cell
- ErbB
- epidermal growth factor
- gamma-secretase
- vascular endothelial growth factor
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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