Upregulation of Connexin 26 Between Keratinocytes of Psoriatic Lesions

Abstract

To assess whether the expression of connexins (Cx) by keratinocytes is altered under conditions of abnormal epidermal differentiation, we have compared Cx26, Cx32, Cx37, Cx40, and Cx43 in the epidermis of 11 psoriatic patients who had not been treated for at least 1 mo and of seven healthy individuals. In all samples of fully mature psoriatic plaques, we have observed a massive expression of Cx26, as judged at both the transcript level (northern blot) and the protein level (immunofluorescence). This protein became consistently detected between keratinocytes of the basal and granular layers at the periphery of psoriatic plaques and in all layers of fully developed psoriatic epidermis, except in regions of parakeratosis. None or a minimal amount of Cx26 was observed in both control and nonlesional regions of psoriatic epidermis. Psoriatic plaques also contained Cx43, the prominent gap junction protein in the interfollicular epidermis of normal human skin. The levels of this protein appeared to be slightly higher in psoriatic than in control skin, as judged at both the transcript level (northern blot) and the protein level (immunofluorescence). Three other connexins (Cx32, Cx37, and Cx40), which are not observed in control interfollicular epidermis, were not induced in either nonlesional or lesional regions of psoriatic skin. The data indicate that selective changes in the normal expression of connexins by keratinocytes are associated with the changes in the proliferation and differentiation program that these cells undergo in psoriasis.

Altered connexin expression and wound healing in the epidermis of connexin-deficient mice

“…Thus, Cx26 and Cx30 both showed the same immediate response to epidermal irritation. Cx26 upregulation has already been reported under hyperproliferative skin conditions (Labarthe et al, 1998). Epidermal wounding results in a loss of the epidermal Ca 2+ .…”

Connexins: a connection with the skin

“…These findings contrast the distinct expression pattern in mouse and rat epidermis, where Cx43 is restricted to basal cells and less differentiated lower spinous cell layers and Cx26 to terminally differentiating spinous and granular cell layers (61,70,80). However, a similar increase and co-expression of Cx26 and Cx43 has been observed when rodent or human epidermis was treated with all-trans retinoic acid or phorbol esters (64,78,81,82). Likewise, analysis of the effect of skin tumor promotors on Cx43, Cx26, and Cx31.1 in Sencar 83 mouse epidermis revealed an induction of Cx26 expression, transiently increased expression of Cx43, and significantly inhibited expression of Cx31.1 (83).…”

“…Another example is provided with the change of Cx expression in psoriasis and other hyperproliferative skin conditions. Despite normal levels of Cx43 expression, there is an impressive up-regulation of Cx26 in psoriatic plaques determined by both cDNA differential display and Northern blot analysis (78,79). Cx26 can be detected by immunostaining throughout all layers of the epidermis, where it is localized at the cell membrane of keratinocytes as well as in the cytoplasm, suggesting a disturbance of Cx26 turnover in psoriatic epidermis (73).…”

On the role of gap junctions in cardiac memory effect

“…Defective connexin proteins are implicated a broad range of human diseasesin cataractogenesis [2], hereditary deafness [3], infertility [4], Psoriasis [5], carcinogenesis [6] impaired inflammatory responses [7], X-linked Charcot-MarieTooth disease [1] etc. Particularly relevant to the present paper is the role of GJs in cardiac disease which have been related to heart failure [9], arrhythmogenesis [10], and atherosclerosis [11].…”