THE VOLUME-REGULATED ANION CHANNEL PROTEIN LRRC8A FOR USE IN ALTERING EPIDERMAL KERATINOCYTE DIFFERENTIATION

摘要

The present invention relates to the leucine-rich repeat-containing protein 8A (LRRC8A), and/or an activator of LRRC8A, for use in the treatment and/or prevention of a skin condition associated with an altered differentiation of keratinocytes. Preferably, the skin condition associated with an altered differentiation of keratinocytes is psoriasis or dermatitis, preferably atopic dermatitis. The present invention further relates to a method of identifying a compound capable of altering the differentiation of keratinocytes, the method comprising the steps of (a) contacting keratinocytes with a test compound and determining the amount of LRRC8A protein or LRRC8A transcript in said keratinocytes; and (b) comparing the amount of LRRC8A protein or LRRC8A transcript determined in step (a) with the amount of LRRC8A protein or LRRC8A transcript in a control not contacted with said test compound, wherein a change in the amount of LRRC8A protein or LRRC8A transcript after contacting the keratinocytes with the test compound indicates that the test compound is capable of altering the differentiation of keratinocytes. Furthermore, the present invention relates to a method of identifying a compound capable of altering the differentiation of keratinocytes, the method comprising the steps of (a) contacting keratinocytes with a test compound and determining the activity of (a) VRAC(s) comprising LRRC8A in said keratinocytes; and (b) comparing the activity determined in step (a) with the activity in a control not contacted with said test compound, wherein a change in the activity of (a) VRAC(s) comprising LRRC8A after contacting the keratinocytes with the test compound indicates that the test compound is capable of altering the differentiation of keratinocytes. The present invention further relates to an inhibitor of the leucine-rich repeat-containing protein 8A (LRRC8A) for use in the treatment and/or prevention of a skin condition selected from skin injury and impaired wound healing, as well as to a cosmetic method for alleviating the effects of a skin condition on the appearance of the skin of an affected individual, the method comprising topically administering an effective amount of (i) leucine-rich repeat-containing protein 8A (LRRC8A); (ii) an activator of LRRC8A; (iii) LRRC8A and an activator of LRRC8A; or (iv) an inhibitor of LRRC8A.