Autocrine nerve growth factor in human keratinocytes

Area of Science:

• Cell Biology
• Dermatology
• Molecular Biology

Background:

• Normal human keratinocytes synthesize and release biologically active nerve growth factor (NGF).
• Keratinocytes express both low-affinity (p75) and high-affinity (TrkA) NGF receptors in the epidermis' basal layer.

Purpose of the Study:

• To investigate the role of the nerve growth factor (NGF) autocrine system in human keratinocyte proliferation and survival.
• To explore the potential involvement of the NGF-TrkA pathway in hyperproliferative skin conditions.

Main Methods:

• Utilized K252, a trk phosphorylation inhibitor, to assess NGF-induced keratinocyte proliferation.
• Investigated keratinocyte proliferation in response to TrkA overexpression and NGF-mimicking antibodies.
• Examined the effects of NGF on keratinocyte apoptosis, including UV-B-induced apoptosis and the role of Bcl-2 family proteins.

Main Results:

• K252 blocked NGF-induced keratinocyte proliferation, and inhibited proliferation in the absence of exogenous NGF.
• Overexpression of TrkA or NGF enhanced keratinocyte proliferation.
• NGF protected keratinocytes from UV-B-induced apoptosis by upregulating Bcl-2 and Bcl-xL, and K252 induced apoptosis in normal keratinocytes, but not in Bcl-2 overexpressing cells.

Conclusions:

• Human keratinocytes possess an autocrine survival system mediated by NGF and its high-affinity receptor, TrkA.
• Elevated NGF and Trk levels in psoriasis suggest a role for this autocrine system in hyperproliferative skin disorders.
• The NGF autocrine system is implicated in the pathogenesis of psoriasis, skin cancer, and other proliferative skin conditions.