Growth hormone promotes lymphangiogenesis.
The lymphatic system plays an important role in inflammation and cancer progression, although the molecular mechanisms involved are poorly understood. As determined using comparative transcriptional profiling studies of cultured lymphatic endothelial cells versus blood vascular endothelial cells, growth hormone receptor was expressed at much higher levels in lymphatic endothelial cells than in blood vascular endothelial cells. These findings were confirmed by quantitative real-time reverse transcriptase-polymerase chain reaction and Western blot analyses. Growth hormone induced in vitro proliferation, sprouting, tube formation, and migration of lymphatic endothelial cells, and the mitogenic effect was independent of vascular endothelial growth factor receptor-2 or -3 activation. Growth hormone also inhibited serum starvation-induced lymphatic endothelial cell apoptosis. No major alterations of lymphatic vessels were detected in the normal skin of bovine growth hormone-transgenic mice. However, transgenic delivery of growth hormone accelerated lymphatic vessel ingrowth into the granulation tissue of full-thickness skin wounds, and intradermal delivery of growth hormone resulted in enlargement and enhanced proliferation of cutaneous lymphatic vessels in wild-type mice. These results identify growth hormone as a novel lymphangiogenic factor.
Banziger-Tobler
Nadja Erika
NE
Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Wolfgang-Pauli-Str. 10, HCI H303, CH-8093 Zurich, Switzerland.
Halin
Cornelia
C
Kajiya
Kentaro
K
Detmar
Michael
M
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004729:Endothelium, Lymphatic / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D013006:Growth Hormone / Q000494:pharmacology / Q000502:physiology*; D019382:Human Growth Hormone / Q000494:pharmacology; D006801:Humans; D007231:Infant, Newborn; D042583:Lymphangiogenesis / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D012879:Skin Physiological Phenomena
D002352:Carrier Proteins; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D013006:Growth Hormone; C051815:somatotropin-binding protein