Ann Dermatol.  2015 Aug;27(4):364-370. 10.5021/ad.2015.27.4.364.

Protease-Activated Receptor-2 Is Associated with Terminal Differentiation of Epidermis and Eccrine Sweat Glands

Affiliations
  • 1Department of Anesthesiology and Pain Medicine, Chungnam National University School of Medicine, Daejeon, Korea.
  • 2Department of Anatomy, Chungnam National University School of Medicine, Daejeon, Korea. yhlee@cnu.ac.kr
  • 3Department of Dermatology, Chungnam National University School of Medicine, Daejeon, Korea.
  • 4Department of Physiology, Chungnam National University School of Medicine, Daejeon, Korea.
  • 5Seoul Neurology Clinic, Nonsan, Korea.
  • 6Department of Plastic Surgery, Konyang University Hospital, Daejeon, Korea.

Abstract

BACKGROUND
Protease-activated receptor 2 (PAR-2) participates in various biological activities, including the regulation of epidermal barrier homeostasis, inflammation, pain perception, and melanosome transfer in the skin.
OBJECTIVE
To evaluate the basic physiological role of PAR-2 in skin.
METHODS
We investigated PAR-2 expression in human epidermis, skin tumors, and cultured epidermal cells using western blot and immunohistochemical analysis. Additionally, we examined the effect of the PAR-2 agonist, SLIGRL-NH2, on cultured keratinocytes.
RESULTS
Strong PAR-2 immunoreactivity was observed in the granular layer of normal human skin and the acrosyringium of the eccrine sweat glands. In contrast, weak PAR-2 immunoreactivity was seen in the granular layer of callused skin and in the duct and gland cells of the eccrine sweat glands. Interestingly, PAR-2 immunoreactivity was very weak or absent in the tumor cells of squamous cell carcinoma (SCC) and syringoma. PAR-2 was detected in primary keratinocytes and SV-40T-transformed human epidermal keratinocytes (SV-HEKs), an immortalized keratinocyte cell line, but not in SCC12 cells. SV-HEKs that were fully differentiated following calcium treatment displayed higher PAR-2 expression than undifferentiated SV-HEKs. Treatment of cultured SV-HEKs with PAR-2 agonist increased loricrin and filaggrin expression, a terminal differentiation marker.
CONCLUSION
Our data suggest that PAR-2 is associated with terminal differentiation of epidermis and eccrine sweat glands.

Keyword

Eccrine sweat glands; Epidermis; Keratinocytes; Terminal differentiation

MeSH Terms

Blotting, Western
Bony Callus
Calcium
Carcinoma, Squamous Cell
Cell Line
Epidermis*
Homeostasis
Humans
Inflammation
Keratinocytes
Melanosomes
Pain Perception
Receptor, PAR-2
Skin
Sweat Glands*
Sweat*
Syringoma
Calcium
Receptor, PAR-2
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