Overexpression of Transforming Growth Factor α in Psoriatic Epidermis

Abstract

Transforming growth factor alpha (TGF-alpha) is produced by and required for the growth of epithelial cells and is angiogenic in vivo. Since epidermal hyperplasia and angiogenesis are hallmarks of psoriasis, TGF-alpha gene expression was analyzed in epidermal biopsies of normal and psoriatic skin. TGF-alpha messenger RNA and protein are much more abundant in lesional psoriatic epidermis than in normal-appearing skin of psoriatic patients or in normal epidermis. In contrast, messenger RNA levels of transforming growth factor beta 1 (TGF-beta 1), which inhibits epithelial cell growth, are not significantly different in normal, uninvolved, and lesional psoriatic epidermis. Thus, psoriatic epidermal hyperplasia may involve increased expression of a keratinocyte mitogen (TGF-alpha) rather than deficient expression of a growth inhibitor (TGF-beta 1).

Epidermal differentiation: the bare essentials.

“…Several reports have implicated an increase in EGF receptors with epidermal tumorigenesis (Yamamoto et al, 1986;Ozanne et al, 1986). In addition, it was recently reported that psoriatic epidermis contained higher levels of TGF-t~ than normal skin, suggesting that overexpression of TGF-t~ might contribute to hyperproliferative diseases of the skin (Gottlieb et al, 1988;Elder et al, 1989). This hypothesis is an attractive one, although it remains to be shown whether the increase in TGF-o~ in psoriasis is causal or consequential.…”

“…TGF-o~ differs from EGF in that it is synthesized by keratinocytes both in vitro and in vivo (Coffey et al, 1987;Gottlieb et al, 1988;Elder et al, 1989). Since epidermal cells autoregulate their own growth via TGF-tx production, it is perhaps not surprising to find that such control can go awry, leading to uncontrolled growth.…”

Functional interaction between c-Jun and promoter factor Sp1 in epidermal growth factor-induced gene expression of human 12( S )-lipoxygenase

“…TGF␣, which is the natural ligand for EGF receptors present on keratinocytes, is overexpressed in psoriatic skin (9). The increased production of TGF␣ may be an important contribution to keratinocyte hyperplasia, because TGF␣ is a potent mitogen for keratinocytes (9).…”

“…12(S)-HETE may play a significant role in the pathogenesis of some epidermal and epithelial inflammation, because a markedly elevated 12(S)-HETE level was found in psoriatic plague (7). In psoriatic lesions, overexpression of epidermal growth factor (EGF) receptors (8), transforming growth factor-␣ (TGF␣) (9), and 12(S)-lipoxygenase (10) has been reported.…”

Anti-CD11a Ameliorates Disease in the Human Psoriatic Skin–SCID Mouse Transplant Model: Comparison of Antibody to CD11a with Cyclosporin A and Clobetasol Propionate

“…In vitro studies show that lymphocytes interact with keratinocytes through leukocyte function-associated antigen-1 (LFA-1)-intercellular adhesion molecule-1 (ICAM-1) (Dustin et al, 1988). The interaction between keratinocytes, local antigen-presenting cells, and T lymphocytes likely initiates and maintains psoriatic lesions via the induction of cytokines, chemokines, and growth factors such as transforming growth factor-␣ (Austin et al, 1999;Elder et al, 1989;Goebeler et al, 1998;Nickoloff, 1991). Locally derived growth factors also contribute to epidermal hyperplasia in conditions other than psoriasis, for example, in wound healing (Stenn and Malhotra, 1992) and cancer (Gottlieb et al, 1988).…”