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Intra- and extracellular signaling by endothelial neuregulin-1
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2007 (English)In: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 313, no 13, 2896-2909 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2007. Vol. 313, no 13, 2896-2909 p.
Keyword [en]
endothelial cell, ErbB, epidermal growth factor, gamma-secretase, vascular endothelial growth factor
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-150839DOI: 10.1016/j.yexcr.2007.03.042ISI: 000248367300013PubMedID: 17499242OAI: oai:DiVA.org:uu-150839DiVA: diva2:409088
Available from: 2011-04-07 Created: 2011-04-06 Last updated: 2011-04-07Bibliographically approved

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