Signalling via vascular endothelial growth factor receptor-3 is sufficient for lymphangiogenesis in transgenic mice

Veikkola, Tanja; Jussila, Lotta; Makinen, Taija; Karpanen, Terhi; Jeltsch, Michael; Petrova, Tatiana V.; Kubo, Hajime; Thurston, Gavin; McDonald, Donald M.; Achen, Marc G.; Stacker, Steven A.; Alitalo, Kari
March 2001
EMBO Journal;3/15/2001, Vol. 20 Issue 6, p1223
Academic Journal
Vascular endothelial growth factor receptor-3 (VEGFR-3) has an essential role in the development of embryonic blood vessels; however, after midgestation its expression becomes restricted mainly to the developing lymphatic vessels. The VEGFR-3 ligand VEGF-C stimulates lymphangiogenesis in transgenic mice and in chick chorioallantoic membrane. As VEGF-C also binds VEGFR-2, which is expressed in lymphatic endothelia, it is not clear which receptors are responsible for the lymphangiogenic effects of VEGF-C. VEGF-D, which binds to the same receptors, has been reported to induce angiogenesis, but its lymphangiogenic potential is not known. In order to define the lymphangiogenic signalling pathway we have created transgenic mice overexpressing a VEGFR-3-specific mutant of VEGF-C (VEGF-C156S) or VEGF-D in epidermal keratinocytes under the keratin 14 promoter. Both transgenes induced the growth of lymphatic vessels in the skin, whereas the blood vessel architecture was not affected. Evidence was also obtained that these growth factors act in a paracrine manner in vivo. These results demonstrate that stimulation of the VEGFR-3 signal transduction pathway is sufficient to induce specifically lymphangiogenesis in vivo.


Related Articles

  • Neural driven angiogenesis by overexpression of nerve growth factor. Hansen-Algenstaedt, N.; Algenstaedt, P.; Schaefer, C.; Hamann, A.; Wolfram, L.; Cingöz, G.; Kilic, N.; Schwarzloh, B.; Schroeder, M.; Joscheck, C.; Wiesner, L.; Rüther, W.; Ergün, S. // Histochemistry & Cell Biology;Jun2006, Vol. 125 Issue 6, p637 

    Mechanisms regulating angiogenesis are crucial in adjusting tissue perfusion on metabolic demands. We demonstrate that overexpression of nerve growth factor (NGF) in brown adipose tissue (BAT) of NGF-transgenic mice elevates both mRNA and protein levels of vascular endothelial growth factor...

  • Protein Kinase CÉ› Inhibits UVR-Induced Expression of FADD, an Adaptor Protein, Linked to both Fas- and TNFR1-Mediated Apoptosis. Aziz, Moammir Hasan; Sundling, Kaitlin Elizabeth; Dreckschmidt, Nancy Ellen; Verma, Ajit Kumar // Journal of Investigative Dermatology;Aug2009, Vol. 129 Issue 8, p2011 

    Protein kinase C (PKC)É› overexpression in FVB/N transgenic mice sensitized skin to UVR-induced development of squamous cell carcinomas and suppressed formation of sunburn cells, which are DNA-damaged keratinocytes undergoing apoptosis. Here, we elucidated the mechanisms associated with the...

  • VEGF Receptor-2 (Flk-1) Overexpression in Mice Counteracts Focal Epileptic Seizures. Nikitidou, Litsa; Kanter-Schlifke, Irene; Dhondt, Joke; Carmeliet, Peter; Lambrechts, Diether; Kokaia, Mérab // PLoS ONE;Jul2012, Vol. 7 Issue 7, p1 

    Vascular endothelial growth factor (VEGF) was first described as an angiogenic agent, but has recently also been shown to exert various neurotrophic and neuroprotective effects in the nervous system. These effects of VEGF are mainly mediated by its receptor, VEGFR-2, which is also referred to as...

  • Roles of Arrest-Defective Protein 1225 and Hypoxia-Inducible Factor 1α in Tumor Growth and Metastasis. Lee, Mi-Ni; Lee, Shi-Nai; Kim, Se-Hee; Kim, Bora; Jung, Bo-Kyung; Seo, Ji Hae; Park, Ji-Hyeon; Choi, Jae-Hoon; Yim, Sun Hee; Lee, Mi-Ran; Park, Jong-Gil; Yoo, Ji-Young; Kim, Jeong Hun; Lee, Seung-Taek; Kim, Hwan-Mook; Ryeom, Sandra; Kim, Kyu-Won; Oh, Goo Taeg // JNCI: Journal of the National Cancer Institute;3/17/2010, Vol. 102 Issue 6, p426 

    Background: Vascular endothelial growth factor A (VEGFA), a critical mediator of tumor angiogenesis, is a well-characterized target of hypoxia-inducible factor 1 (HIF-1). Murine arrest-defective protein 1A (mARD1A225) acetylates HIF-1α, triggering its degradation, and thus may play a role in...

  • Conditioned Medium from Cultured Human Keratinocytes Has Growth Stimulatory Properties on Different Human Cell Types. Kratz, Gunnar; Hægerstrand, Anders; Dalsgaard, Carl-Johan // Journal of Investigative Dermatology;Dec91, Vol. 97 Issue 6, p1039 

    Evidence for growth-stimulatory properties of keratinocyte-conditioned medium (KCM) on human fibroblasts, endothelial cells, keratinocyte, smooth muscle cells, and a mouse fibroblast cell line (3T3 cells) is presented. On human fibroblasts KCM caused an increase of over 400% in DNA synthesis as...

  • Connective Tissue Growth Factor Induces the Proliferation, Migration, and Tube Formation of Vascular Endothelial Cells In Vitro, and Angiogenesis In Vivo1. Shimo, Tsuyoshi; Nakanishi, Tohru; Nishida, Takashi; Asano, Masahiro; Kanyama, Manabu; Kuboki, Takuo; Tamatani, Takuya; Tezuka, Katsunari; Takemura, Motohide; Matsumura, Tomohiro; Takigawa, Masaharu // Journal of Biochemistry;1999, Vol. 126 Issue 1, p137 

    Connective tissue growth factor (CTGF) is a novel cysteine-rich, secreted protein. Recently, we found that inhibition of the endogenous expression of CTGF by its antisense oligonu-cleotide and antisense RNA suppresses the proliferation and migration of vascular endo-thelial cells. In the present...

  • Activated omentum becomes rich in factors that promote healing and tissue regeneration. Litbarg, Natalia O.; Gudehithlu, Krishnamurthy P.; Sethupathi, Perianna; Arruda, Jose A. L.; Dunea, George; Singh, Ashok K. // Cell & Tissue Research;May2007, Vol. 328 Issue 3, p487 

    In order to study the mechanism by which an omental pedicle promotes healing when applied to an injured site, we injected a foreign body into the abdominal cavity to activate the omentum. One week after the injection, we isolated the omentum and measured blood vessel density, blood content,...

  • The concerted regulatory functions of the transcription factors nuclear factor-1 and upstream stimulatory factor on a composite element in the promoter of the hepatocyte growth factor gene. Jiang, Jie-Gen; Gao, Bin; Zarnegar, Reza // Oncogene;5/31/2000, Vol. 19 Issue 23, p2786 

    Hepatocyte growth factor (HGF) is an important multifunctional cytokine whose gene expression is regulated mainly at the transcriptional level. Previous studies using transgenic mice as well as in vitro analyses showed that a potential regulatory element(s) exists between -260 to -230 bp in the...

  • TGF-β1 promotes microglial amyloid-β clearance and reduces plaque burden in transgenic mice. Wyss-Coray, Tony; Lin, Carol; Yan, Fengrong; Yu, Gui-Qiu; Rohde, Michelle; McConlogue, Lisa; Masliah, Eliezer; Mucke, Lennart // Nature Medicine;May2001, Vol. 7 Issue 5, p612 

    Abnormal accumulation of the amyloid-β peptide (Aβ) in the brain appears crucial to pathogenesis in all forms of Alzheimer disease (AD), but the underlying mechanisms in the sporadic forms of AD remain unknown. Transforming growth factor β1 (TGF-β1), a key regulator of the brain's...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics