| 1. |
- Iivanainen, Erika, et al.
(författare)
-
Intra- and extracellular signaling by endothelial neuregulin-1
- 2007
-
Ingår i: Experimental Cell Research. - : Elsevier BV. - 0014-4827 .- 1090-2422. ; 313:13, s. 2896-2909
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 2. |
- Kubo, Hajime, et al.
(författare)
-
Blockade of vascular endothelial growth factor receptor-3 signaling inhibits fibroblast growth factor-2-induced lymphangiogenesis in mouse cornea.
- 2002
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 99:13
-
Tidskriftsartikel (refereegranskat)abstract
- Vascular endothelial growth factor receptor-3 (VEGFR-3) is a major mediator of lymphangiogenesis. Recently, VEGFR-3 ligands, VEGF-C, and VEGF-D were reported to promote tumor lymphangiogenesis and lymphatic metastasis, and these processes were inhibited by blocking of the VEGFR-3-signaling pathway. Here, we have adapted the mouse corneal angiogenesis assay to study potential lymphangiogenic factors and inhibitors. Immunohistochemical analysis with lymphatic endothelial markers showed that VEGF-C induces lymphatic as well as blood vessel growth in the cornea. By contrast, VEGF induced angiogenesis but not lymphangiogenesis. Fibroblast growth factor-2 (FGF-2) stimulated both lymphangiogenesis and angiogenesis. FGF-2 up-regulated VEGF-C expression in vascular endothelial and perivascular cells. Furthermore, administration of blocking anti-VEGFR-3 antibodies inhibited the FGF-2-induced lymphangiogenesis. These findings show that VEGFR-3 can mediate lymphangiogenesis induced by other growth factors. Because increased expression of FGF-2 and VEGF-C has been associated with lymphatic metastasis, our results provide a potential strategy for the inhibition of lymphatic metastasis in cancer therapy.
|
|
| 3. |
- Xue, Yuan, et al.
(författare)
-
FOXC2 controls Ang-2 expression and modulates angiogenesis, vascular patterning, remodeling, and functions in adipose tissue
- 2008
-
Ingår i: Proceedings of The National Academy of Sciences of The United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 105:29, s. 10167-10172
-
Tidskriftsartikel (refereegranskat)abstract
- Adipogenesis is spatiotemporally coupled to angiogenesis throughout adult life, and the interplay between these two processes is communicated by multiple factors. Here we show that in a transgenic mouse model, increased expression of forkhead box C2 (FOXC2) in the adipose tissue affects angiogenesis, vascular patterning, and functions. White and brown adipose tissues contain a considerably high density of microvessels appearing as vascular plexuses, which show redistribution of vascular smooth muscle cells and pericytes. Dysfunction of these primitive vessels is reflected by impairment of skin wound healing. We further provide a mechanistic insight of the vascular phenotype by showing that FOXC2 controls Ang-2 expression by direct activation of its promoter in adipocytes. Remarkably, an Ang-2-specific antagonist almost completely reverses this vascular phenotype. Thus, the FOXC2–Ang-2 signaling system is crucial for controlling adipose vascular function, which is part of an adaptation to increased adipose tissue metabolism.
|
|
