NGF and its receptors TrkA and p75NTR in the epithelium of oral lichen.
BACKGROUND
Nerve growth factor (NGF) can through its receptors TrkA and p75(NTR) convey signals for cell survival, differentiation and death. The aim of this study was to examine whether NGF can play a role in the pathology of oral lichen (OL).


METHODS
Sections from biopsies taken from patients with erythematous (ERY) OL and from volunteers with normal oral mucosa (NOM) were immunostained with antibodies against NGF, proNGF, TrkA, phosphorylated Trk, p75(NTR) and phosphorylated Akt (pAkt) and expression of RNA coding for proNGF/NGF was investigated by in situ hybridization.


RESULTS
Both in ERY OL and NOM, cytoplasmic staining for NGF was seen in granular and upper spinous cell layers of the epithelium, whereas proNGF staining was seen in all epithelial cell layers. In situ hybridization showed that the proNGF protein was produced in the same cell layers. In OL, strong cytoplasmic stainings for TrkA and activated Trk (pTrk) were observed in all epithelial cell layers while these stainings were only weak in NOM. Basal keratinocytes in OL showed no or only weak cytoplasmic staining for p75(NTR), but in NOM there was a clear cell membrane staining. In OL, strong cytoplasmic and intermittent nuclear staining for pAkt was observed in spinous, granular and superficial layers, while basal and parabasal keratinocytes were negative. This staining was weak or absent in the entire epithelium of NOM.


CONCLUSIONS
TrkA upregulation and activation in OL is one of the pathways that can activate pAkt and thereby rescue epithelial cells from untimely cell death.
Hayashi
Katsuhiko
K
Department of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway.
Karatsaidis
Andreas
A
Schreurs
Olav
O
Bjørnland
Tore
T
Sugisaki
Masashi
M
Schenck
Karl
K
D000328:Adult; D017209:Apoptosis / Q000502:physiology; D016022:Case-Control Studies; D002470:Cell Survival / Q000502:physiology; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D015603:Keratinocytes / Q000378:metabolism; D017676:Lichen Planus, Oral / Q000378:metabolism* / Q000473:pathology*; D008875:Middle Aged; D009061:Mouth Mucosa / Q000737:chemistry; D020932:Nerve Growth Factor / Q000096:biosynthesis*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D011498:Protein Precursors / Q000096:biosynthesis; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis; D020917:Receptor, trkA / Q000096:biosynthesis*; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis*; D015854:Up-Regulation
C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D011498:Protein Precursors; D017475:Receptors, Nerve Growth Factor; C061397:pro-nerve growth factor, human; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D051057:Proto-Oncogene Proteins c-akt