Dataset Information

NGF Modulates trkANGFR/p75NTR in ?SMA-Expressing Conjunctival Fibroblasts from Human Ocular Cicatricial Pemphigoid (OCP).

ABSTRACT: In a previous study, we reported the upregulation of Nerve Growth Factor (NGF) and trkANGFR expression in Ocular Cicatricial Pemphigoid (OCP), an inflammatory and remodeling eye disease. Herein, we hypothesize a potential NGF-driven mechanism on fibroblasts (FBs) during OCP remodeling events. To verify, human derived OCP-FBs were isolated and characterized either at baseline or after NGF exposure.Conjunctival biopsies were obtained from 7 patients having OCP and 6 control subjects (cataract surgery). Both conjunctivas and primary FB cultures were characterised for ?SMA, NGF and trkANGFR/p75NTR expression. Subcultures were exposed to NGF and evaluated for ?SMA, NGF, trkANGFR/p75NTR expression as well as TGF?1/IL4 release. For analysis, early and advanced subgroups were defined according to clinical parameters.OCP-conjunctivas showed ?SMA-expressing FBs and high NGF levels. Advanced OCP-FBs showed higher ?SMA expression associated with higher p75NTR and lower trkANGFR expression, as compared to early counterparts. ?SMA expression was in keeping with disease severity and correlated to p75NTR. NGF exposure did not affect trkANGFR levels in early OCP-FBs while decreased both ?SMA/p75NTR expression and TGF?1/IL4 release. These effects were not observed in advanced OCP-FBs.Taken together, these data are suggestive for a NGF/p75NTR task in the potential modulation of OCP fibrosis and encourages further studies to fully understand the underlying mechanism occurring in fibrosis. NGF/p75NTR might be viewed as a potential therapeutic target.

SUBMITTER: Micera A

PROVIDER: S-EPMC4646573 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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NGF Modulates trkANGFR/p75NTR in αSMA-Expressing Conjunctival Fibroblasts from Human Ocular Cicatricial Pemphigoid (OCP).

Micera Alessandra A Stampachiacchiere Barbara B Di Zazzo Antonio A Sgrulletta Roberto R Cortes Magdalena M Normando Eduardo Maria EM Lambiase Alessandro A Bonini Stefano S Bonini Stefano S

PloS one 20151116 11

<h4>Objective</h4>In a previous study, we reported the upregulation of Nerve Growth Factor (NGF) and trkANGFR expression in Ocular Cicatricial Pemphigoid (OCP), an inflammatory and remodeling eye disease. Herein, we hypothesize a potential NGF-driven mechanism on fibroblasts (FBs) during OCP remodeling events. To verify, human derived OCP-FBs were isolated and characterized either at baseline or after NGF exposure.<h4>Materials and methods</h4>Conjunctival biopsies were obtained from 7 patients ...[more]

PMID: 26569118

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Project description:BACKGROUND:Nerve growth factor (NGF) and its receptors, tropomyosin receptor kinase A (TrkA) and pan-neurotrophin receptor p75 (p75NTR), are known to play bidirectional roles between the immune and nervous system. There are only few studies with inconclusive results concerning the expression pattern and role of NGF, TrkA, and p75NTR (NGF system) under the neuroinflammatory conditions in multiple sclerosis (MS) and its mouse model, the experimental autoimmune encephalomyelitis (EAE). The aim of this study is to investigate the temporal expression in different cell types of NGF system in the central nervous system (CNS) during the EAE course. METHODS:EAE was induced in C57BL/6 mice 6-8?weeks old. CNS tissue samples were collected on specific time points: day 10 (D10), days 20-22 (acute phase), and day 50 (chronic phase), compared to controls. Real-time PCR, Western Blot, histochemistry, and immunofluorescence were performed throughout the disease course for the detection of the spatio-temporal expression of the NGF system. RESULTS:Our findings suggest that both NGF and its receptors, TrkA and p75NTR, are upregulated during acute and chronic phase of the EAE model in the inflammatory lesions in the spinal cord. NGF and its receptors were co-localized with NeuN+ cells, GAP-43+ axons, GFAP+ cells, Arginase1+ cells, and Mac3+ cells. Furthermore, TrkA and p75NTR were sparsely detected on CNPase+ cells within the inflammatory lesion. Of high importance is our observation that despite EAE being a T-mediated disease, only NGF and p75NTR were shown to be expressed by B lymphocytes (B220+ cells) and no expression on T lymphocytes was noticed. CONCLUSION:Our results indicate that the components of the NGF system are subjected to differential regulation during the EAE disease course. The expression pattern of NGF, TrkA, and p75NTR is described in detail, suggesting possible functional roles in neuroprotection, neuroregeneration, and remyelination by direct and indirect effects on the components of the immune system.

Dataset Information

NGF Modulates trkANGFR/p75NTR in ?SMA-Expressing Conjunctival Fibroblasts from Human Ocular Cicatricial Pemphigoid (OCP).

Publications

NGF Modulates trkANGFR/p75NTR in αSMA-Expressing Conjunctival Fibroblasts from Human Ocular Cicatricial Pemphigoid (OCP).

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