Altered expression of angiopoietins and Tie2 endothelium receptor in psoriasis.
Psoriasis is a chronic inflammatory skin disease in which epidermal proliferation is closely associated with excessive microvascular expansion within the papillary dermis. Angiopoietins have recently been identified as the major ligands of the endothelial- specific receptor Tie2. Angiopoietin 1 induces Tie2 signaling as a receptor activator and maintains blood vessel formation, whereas angiopoietin 2 destabilizes vessels by blocking Tie2 signaling as an antagonist of angiopoietin 1 and acts with vascular endothelial growth factor to initiate angiogenesis. In this study we examined the potential role of angiopoietins and the Tie2 receptor in vascular changes of psoriasis. Angiopoietin 1, angiopoietin 2, and Tie2 were upregulated in involved psoriasis skin compared to uninvolved psoriasis skin, healthy skin, and chronic spongiotic dermatitis skin. Angiopoietin 1 was expressed by stromal cells in the highly vascularized papillary dermis of involved psoriasis skin. Angiopoietin 2 was expressed by endothelial cells in the vicinity of the proliferating epidermis that abundantly expressed vascular endothelial growth factor. Vascular endothelial growth factor and basic fibroblast growth factor, which were overexpressed in involved psoriasis skin, enhanced angiopoietin 2 and Tie2 expression in dermal microvascular endothelial cell cultures. Thus, our findings suggest that upregulation of angiopoietin 1, angiopoietin 2, and Tie2 is closely associated with the development of microvascular proliferation in psoriasis, and that the angiopoietin-Tie2 system may act coordinately with vascular endothelial growth factor and basic fibroblast growth factor to promote neovascularization in psoriasis. Moreover, successful antipsoriatic treatment was accompanied by noticeable reduction of angiopoietin 2 expression, suggesting that alteration of angiopoietin 2 expression may be particularly important in controlling vascular proliferation in the treatment of psoriasis.
Kuroda
K
K
Department of Dermatology, Mount Sinai School of Medicine, New York, New York, USA. krkuro@ceres.ocn.ne.jp
Sapadin
A
A
Shoji
T
T
Fleischmajer
R
R
Lebwohl
M
M
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D016207:Cytokines / Q000502:physiology; D003879:Dermatologic Agents / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D009539:Nicotinic Acids / Q000627:therapeutic use; D011701:PUVA Therapy; D011506:Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D011565:Psoriasis / Q000188:drug therapy / Q000378:metabolism*; D042787:Receptor, TIE-2; D012867:Skin / Q000378:metabolism; D014018:Tissue Distribution; D012176:Retinoids
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D016207:Cytokines; D003879:Dermatologic Agents; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D009539:Nicotinic Acids; D011506:Proteins; D011518:Proto-Oncogene Proteins; D042787:Receptor, TIE-2; C105373:MEN1 protein, human; C086827:tazarotene; D012176:Retinoids