TY - JOUR
T1 - Notch signaling
T2 - Its role in epidermal homeostasis and in the pathogenesis of skin diseases
AU - Okuyama, Ryuhei
AU - Tagami, Hachiro
AU - Aiba, Setsuya
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2008/3
Y1 - 2008/3
N2 - Skin undergoes self-renewal throughout life. Terminally differentiated keratinocytes, namely the corneocytes, are continually shed from the surface of the skin, whereas immature cells produce progeny that proceed through the differentiation process. Notch signaling controls a number of cellular processes including cell fate decision, proliferation, differentiation and survival/apoptosis. Hence, Notch and its ligands are expressed in multiple tissues including the skin, where they are abundantly expressed in the epidermis. Notch activation results in the promotion of growth arrest and the onset of differentiation, therefore suggesting that specific Notch activation may regulate skin homeostasis by balancing these processes, i.e. Notch signaling functions as a molecular switch that controls the transition of cells between skin layers during the epidermal differentiation process. Recent advances in the study of Notch signaling have confirmed that there is cross-talk between the Notch signaling pathway and a variety of other signaling molecules including Sonic hedgehog (Shh), β-catenin and the p53 family member, p63. The absence of Notch activity allows Wnt and Shh signaling to persist in a tissue where they are normally repressed. In addition, Notch counteracts the action of p63 to maintain immature cell characteristics. However, aberrant Notch signaling results in the development of psoriasis and skin cancers such as squamous cell carcinoma, basal cell carcinoma and malignant melanoma. Future efforts to further define how Notch controls cell proliferation and differentiation may lead to the application of Notch in new therapies for various skin diseases.
AB - Skin undergoes self-renewal throughout life. Terminally differentiated keratinocytes, namely the corneocytes, are continually shed from the surface of the skin, whereas immature cells produce progeny that proceed through the differentiation process. Notch signaling controls a number of cellular processes including cell fate decision, proliferation, differentiation and survival/apoptosis. Hence, Notch and its ligands are expressed in multiple tissues including the skin, where they are abundantly expressed in the epidermis. Notch activation results in the promotion of growth arrest and the onset of differentiation, therefore suggesting that specific Notch activation may regulate skin homeostasis by balancing these processes, i.e. Notch signaling functions as a molecular switch that controls the transition of cells between skin layers during the epidermal differentiation process. Recent advances in the study of Notch signaling have confirmed that there is cross-talk between the Notch signaling pathway and a variety of other signaling molecules including Sonic hedgehog (Shh), β-catenin and the p53 family member, p63. The absence of Notch activity allows Wnt and Shh signaling to persist in a tissue where they are normally repressed. In addition, Notch counteracts the action of p63 to maintain immature cell characteristics. However, aberrant Notch signaling results in the development of psoriasis and skin cancers such as squamous cell carcinoma, basal cell carcinoma and malignant melanoma. Future efforts to further define how Notch controls cell proliferation and differentiation may lead to the application of Notch in new therapies for various skin diseases.
KW - Cross-talk
KW - Differentiation
KW - Keratinocyte
KW - Notch
KW - Oncogenesis
KW - Psoriasis
UR - http://www.scopus.com/inward/record.url?scp=38749101987&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=38749101987&partnerID=8YFLogxK
U2 - 10.1016/j.jdermsci.2007.05.017
DO - 10.1016/j.jdermsci.2007.05.017
M3 - Review article
C2 - 17624739
AN - SCOPUS:38749101987
VL - 49
SP - 187
EP - 194
JO - Journal of Dermatological Science
JF - Journal of Dermatological Science
SN - 0923-1811
IS - 3
ER -