VDR mediated calcitriol signalling related to 6 1- and 6 4-Integrin

Basal keratinocytes are attachment-dependent cells, interacting with their surface to neighbouring cells e.g. integrin mediated mechanisms. Their proliferation and differentiation is regulated by 1,25-dihydroxyvitaminD3, that also influences the mRNA expression of integrins especially, heterodimers between different integrin types. Integrin 6 is able to form heterodimers in keratinocytes with either 1 or 4. Using real-time expriments, the influence of 1,25-dihydroxyvitaminD3 on integrin gene-expression in human HaCaTs was studied in vitro. Additionally we performed VDR promoter binding studies using ChIP assays. It was hypothized that calcitriol regulates the cellular concentration of integrins and shifts the equilibrium of 6, 1 and 4 heterodimers. The 6/ 4 heterodimer is preferred in HaCat cells in the presence of calcitriol and 6/ 1 heterodimer suffers from the compound. Since 6/ 4 heterodimers are responsible for adhesion of basal keratinocytes to the underlying matrix in the human skin, we conclude an increased adhesion capacity of basal keratinocytes to the basal lamina in the presence of calcitriol.

Autorentext

2009-2011 Postgraduelles Studium (Dr. Scient med.) der medizinischen Wissenschaft, Paracelsus medizinische Privatuniversität Salzburg 2007-2009 Master-Studium: Genetik, Paris-Lodron Universität Salzburg, Österreich 2004-2007 Bakkalaureat-Studium: Genetik und Molekularbiologie Paris-Lodron Universität Salzburg, Österreich