Betacellulin (BTC) is a peptide ligand that belongs to the epidermal growth factor family, the members of which are implicated in skin morphogenesis, homeostasis, repair, and angiogenesis; however, the role of BTC in regulation of skin barrier remains unknown so far. To examine the role of BTC in skin barrier function, we analysed data from two independent Gene Expression Omnibus (GEO) datasets and evaluated the effects of BTC on primary human keratinocytes using real-time PCR, Western blot and transepidermal electrical resistance (TER), a functional parameter to monitor the tight junction barrier. We found that the gene expression of BTC was higher in skin lesions from patients with atopic dermatitis (AD), and this expression upregulated following biological treatments, suggesting that the levels of BTC in the skin might be a biomarker for the therapy of AD. Moreover, following stimulation of keratinocytes with different cytokines, we observed that the mRNA expression of BTC was significantly and exclusively inhibited by the Th2 cytokines such as IL-4 and IL-13, which play a pivotal role in the pathogenesis of AD. Furthermore, the specific inhibitors of epidermal growth factor receptor and protein kinase C abolished the BTC-mediated improvement of tight junction-related proteins, including claudin-1 and ZO-1 and suppressed TER in keratinocyte monolayers. Importantly, BTC recovered the increased tight junction permeability in IL-4/IL-13-treated keratinocytes. Together, we propose that BTC might be a novel potential biomarker and therapeutic target for the treatment of skin diseases characterized by overproduction of Th2 cytokines and dysfunctional skin barrier such as AD.

ESDR192 - Betacellulin alleviates Th2 cytokine-mediated impairment of skin tight junction barrier through epidermal growth factor receptor and protein kinase C pathway

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.