Somatostatin regulates tight junction function and composition in human keratinocytes.

Abstract:

:Somatostatin (SST) is a regulatory peptide hormone that acts through five different G protein-coupled receptors (SSTR1-5). Whereas expression of all five SSTR subtypes in epidermis has been shown, the biological relevance of the SST/SSTR system in the skin is completely unknown. We show here that SST is expressed in human skin and is present in a subset of Merkel cells and dendritic cells as well as in keratinocytes. We focused further on the somatostatin receptor subtype 3 (SSTR3) and its interacting protein MUPP1, as both were found to be localized at cellular junctions in epidermal keratinocytes. MUPP1 is a component of tight junctions (TJs); these cell-cell junctions contribute to barrier function of the paracellular pathway in cultured keratinocytes. We provide evidence that SSTR3 and MUPP1 interact in primary cultured human keratinocytes at high Ca(2+) conditions. Interestingly, SST, presumably via SSTR3/MUPP1, regulates TJ permeability in cultured keratinocytes. During long-term treatment of human keratinocytes, SST also affects the expression of distinct TJ proteins such as claudin-4. Our data are the first example of a peptide hormone regulating TJ functionality and composition in human keratinocytes, suggesting that control via peptide hormones provides the possibility to regulate the TJ barrier characteristics of the skin.

journal_name

Exp Dermatol

journal_title

Experimental dermatology

authors

Vockel M,Breitenbach U,Kreienkamp HJ,Brandner JM

doi

10.1111/j.1600-0625.2010.01101.x

subject

Has Abstract

pub_date

2010-10-01 00:00:00

pages

888-94

issue

10

eissn

0906-6705

issn

1600-0625

pii

EXD1101

journal_volume

19

pub_type

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