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


CONCLUSIONS
Our data suggest that PAR-2 is associated with terminal differentiation of epidermis and eccrine sweat glands.
Department of Anesthesiology and Pain Medicine, Chungnam National University School of Medicine, Daejeon, Korea.
Yong-Sup
YS
Shin
Department of Anatomy, Chungnam National University School of Medicine, Daejeon, Korea.
Hyung Won
HW
Kim
Department of Dermatology, Chungnam National University School of Medicine, Daejeon, Korea.
Chang Deok
CD
Kim
Department of Physiology, Chungnam National University School of Medicine, Daejeon, Korea.
Hyun-Woo
HW
Kim
Seoul Neurology Clinic, Nonsan, Korea.
Jin Woon
JW
Park
Department of Plastic Surgery, Konyang University Hospital, Daejeon, Korea.
Sunggyun
S
Jung
Department of Dermatology, Chungnam National University School of Medicine, Daejeon, Korea.
Jeung-Hoon
JH
Lee
Department of Anesthesiology and Pain Medicine, Chungnam National University School of Medicine, Daejeon, Korea.
Young-Kwon
YK
Ko
Department of Anatomy, Chungnam National University School of Medicine, Daejeon, Korea.
Young Ho
YH
Lee
Eccrine sweat glands; Epidermis; Keratinocytes; Terminal differentiation