Title: Nerve growth factor and its role in epidermal homeostasis
Abstract: Nerve growth factor (NGF) belongs to the neurotrophin (NT) family which also includes brain‐derived neurotrophic factor (BDNF), neurotrophin‐3 (NT‐3) and NT‐4/5. Human keratinocytes synthesize and release all NT and express both the low‐ (p75NTR) and the high‐affinity receptor (trk). Keratinocyte stem cells (KSCs) express higher levels of NGF as compared with young transit amplifying (TA) cells, while NGF levels are almost undetectable in TA cells. While trk is expressed in all basal keratinocytes in a homogeneous pattern, p75 is expressed only in a subpopulation of basal keratinocytes. p75 is strongly expressed in young TA cells, whereas it is scarcely visible in TA cells and absent in KSCs. Moreover, Ca ++ strongly enhances p75 expression in subconfluent cells. NGF stimulates keratinocyte proliferation and protects keratinocytes from spontaneous and UVB‐induced apoptosis. These activities are performed through trk receptor, while the role of p75 is more controversial. p75 belongs to the TNF receptor superfamily, and it shares with other members of this family a death domain which signals apoptosis upon binding to the ligands. BDNF or NT‐4 induces keratinocyte apoptosis through p75, while the trk inhibitor K252 augments cell death in p75‐overexpressing keratinocytes. BDNF also activates c‐JUN kinase (JNK) in p75‐transfected keratinocytes. Taken together, these data point to a dual role of NT in epidermal homeostasis.
Publication Year: 2004
Publication Date: 2004-09-01
Language: en
Type: article
Indexed In: ['crossref']
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