Somatostatin regulates tight junction function and composition in human keratinocytes.
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.
Vockel
Matthias
M
Department of Dermatology and Venerology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
Breitenbach
Ute
U
Kreienkamp
Hans-Jürgen
HJ
Brandner
Johanna M
JM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D057167:Claudins / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D010539:Permeability; D012333:RNA, Messenger / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism*; D013004:Somatostatin / Q000235:genetics / Q000378:metabolism*; D019108:Tight Junctions / Q000378:metabolism*; D055815:Young Adult
D002352:Carrier Proteins; D057167:Claudins; C111442:MPDZ protein, human; D008565:Membrane Proteins; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; C103631:somatostatin receptor 3; D013004:Somatostatin; D000242:Cyclic AMP; D002118:Calcium