Protease-Activated Receptor-2 Is Associated with Terminal Differentiation of Epidermis and Eccrine Sweat Glands
1
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
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.
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.
참고문헌 (28)
- Demerjian M, "Acute modulations in permeability barrier function regulate epidermal cornification:role of caspase-14 and the protease-activated receptor type 2", Am J Pathol, 172, pp.86~97 (2008)
- Jeong SK, "Mite and cockroach allergens activate protease-activated receptor 2 and delay epidermal permeability barrier recovery", J Invest Dermatol, 128, pp.1930~1939 (2008)
- Hachem JP, "Sustained serine proteases activity by prolonged increase in pH leads to degradation of lipid processing enzymes and profound alterations of barrier function and stratum corneum integrity", J Invest Dermatol, 125, pp.510~520 (2005)
- Feingold KR, "The regulation of permeability barrier homeostasis", J Invest Dermatol, 127, pp.1574~1576 (2007)
- Yamasaki K, "Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea", Nat Med, 13, pp.975~980 (2007)
- Seeliger S, "Proinflammatory role of proteinaseactivated receptor-2 in humans and mice during cutaneous inflammation in vivo", FASEB J, 17, pp.1871~1885 (2003)
- Kim JY, "Proteaseactivated receptor-2 activates NQO-1 via Nrf2 stabilization in keratinocytes", J Dermatol Sci, 74, pp.48~55 (2014)
- Scott G, "Protease-activated receptor 2, a receptor involved in melanosome transfer, is upregulated in human skin by ultraviolet irradiation", J Invest Dermatol, 117, pp.1412~1420 (2001)
- Grant AD, "Protease-activated receptor 2 sensitizes the transient receptor potential vanilloid 4 ion channel to cause mechanical hyperalgesia in mice", J Physiol, 578, pp.715~733 (2007)
- Ding-Pfennigdorff D, "Stimulation of PAR-2 excites and sensitizes rat cutaneous C-nociceptors to heat", Neuroreport, 15, pp.2071~2075 (2004)
- Ando H, "Melanosomes are transferred from melanocytes to keratinocytes through the processes of packaging, release, uptake, and dispersion", J Invest Dermatol, 132, pp.1222~1229 (2012)
- Ando H, "Keratinocytes in culture accumulate phagocytosed melanosomes in the perinuclear area", Pigment Cell Melanoma Res, 23, pp.129~133 (2010)
- Rattenholl A, "Proteinase-activated receptor-2 in the skin: receptor expression, activation and function during health and disease", Drug News Perspect, 21, pp.369~381 (2008)
- Steinhoff M, "Proteinase-activated receptor-2 in human skin: tissue distribution and activation of keratinocytes by mast cell tryptase", Exp Dermatol, 8, pp.282~294 (1999)
- Nemes Z, "Bricks and mortar of the epidermal barrier", Exp Mol Med, 31, pp.5~19 (1999)
- Komatsu N, "Multiple tissue kallikrein mRNA and protein expression in normal skin and skin diseases", Br J Dermatol, 153, pp.274~281 (2005)
- Kishibe M, "Kallikrein 8 is involved in skin desquamation in cooperation with other kallikreins", J Biol Chem, 282, pp.5834~5841 (2007)
- Santulli RJ, "Evidence for the presence of a proteaseactivated receptor distinct from the thrombin receptor in human keratinocytes", Proc Natl Acad Sci U S A, 92, pp.9151~9155 (1995)
- Derian CK, "Differential regulation of human keratinocyte growth and differentiation by a novel family of protease-activated receptors", Cell Growth Differ, 8, pp.743~749 (1997)
- Bovell DL, "PAR-2 receptor-induced effects on human eccrine sweat gland cells", J Med Invest, 56(Suppl), pp.371~374 (2009)
- Bovell DL, "Activation of chloride secretion via proteinase-activated receptor 2 in a human eccrine sweat gland cell line--NCL-SG3", Exp Dermatol, 17, pp.505~511 (2008)
- Rattenholl A, "Proteinase-activated receptor-2 (PAR2):a tumor suppressor in skin carcinogenesis", J Invest Dermatol, 127, pp.2245~2252 (2007)
- Yoon HK, "Prediction and evaluation of protein-protein interaction in keratinocyte differentiation", Biochem Biophys Res Commun, 377, pp.662~667 (2008)
- Kawachi Y, "Superficial epithelioma with sebaceous differentiation:immunohistochemical study of keratinocyte differentiation markers", Eur J Dermatol, 21, pp.1016~1017 (2011)
- Kim SH, "Callus formation is associated with hyperproliferation and incomplete differentiation of keratinocytes, and increased expression of adhesion molecules", Br J Dermatol, 163, pp.495~501 (2010)
- Jeon GA, "Global gene expression profiles of human head and neck squamous carcinoma cell lines", Int J Cancer, 112, pp.249~258 (2004)
- Seung Ju Back, "Epigenetic Modulation of Gene Expression during Keratinocyte Differentiation", Annals of Dermatology, 24(3), pp.261~266 (2012), 대한피부과학회[DOI]
- Gazel A, "Transcriptional profiling defines the roles of ERK and p38 kinases in epidermal keratinocytes", J Cell Physiol, 215, pp.292~308 (2008)