Somatostatin regulates tight junction function and composition in human keratinocytes

Exp Dermatol. 2010 Oct;19(10):888-94. doi: 10.1111/j.1600-0625.2010.01101.x.


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.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Calcium / metabolism
  • Calcium / pharmacology
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cells, Cultured
  • Claudins / metabolism
  • Cyclic AMP / metabolism
  • Female
  • Humans
  • Keratinocytes / cytology*
  • Keratinocytes / metabolism*
  • Male
  • Membrane Proteins
  • Middle Aged
  • Permeability
  • RNA, Messenger / metabolism
  • Receptors, Somatostatin / genetics
  • Receptors, Somatostatin / metabolism*
  • Somatostatin / genetics
  • Somatostatin / metabolism*
  • Tight Junctions / metabolism*
  • Young Adult


  • Carrier Proteins
  • Claudins
  • MPDZ protein, human
  • Membrane Proteins
  • RNA, Messenger
  • Receptors, Somatostatin
  • somatostatin receptor 3
  • Somatostatin
  • Cyclic AMP
  • Calcium