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

• Published in: PloS one Vol. 10; no. 11; p. e0142737
• Main Authors: Micera, Alessandra, Stampachiacchiere, Barbara, Di Zazzo, Antonio, Sgrulletta, Roberto, Cortes, Magdalena, Normando, Eduardo Maria, Lambiase, Alessandro, Bonini, Stefano
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 2015; Public Library of Science (PLoS)
• Subjects: Actins - metabolism; Aged; Aged, 80 and over; Biopsy; Cataracts; College campuses; Conjunctiva - metabolism; Conjunctiva - pathology; Disease; Exposure; Female; Fibroblasts; Fibroblasts - metabolism; Fibrosis; Flow Cytometry; Gene Expression Regulation; Growth factors; Humans; Immunoglobulins; Inflammation; Inflammatory diseases; Interleukin 4; Interleukin-4 - metabolism; Life assessment; Male; Microscopy, Confocal; Middle Aged; Mucous membrane pemphigoid; Nerve growth factor; Nerve Growth Factor - metabolism; Nerve Tissue Proteins - metabolism; Pemphigoid; Pemphigoid, Benign Mucous Membrane - metabolism; Phenotype; Real-Time Polymerase Chain Reaction; Receptor, trkA - metabolism; Receptors, Nerve Growth Factor - metabolism; Subgroups; Surgery; Therapeutic applications; Transforming Growth Factor beta1 - metabolism; Transforming growth factor-b1; United Kingdom > UK; Italy; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0142737

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 αSMA, NGF and trkANGFR/p75NTR expression. Subcultures were exposed to NGF and evaluated for αSMA, NGF, trkANGFR/p75NTR expression as well as TGFβ1/IL4 release. For analysis, early and advanced subgroups were defined according to clinical parameters. OCP-conjunctivas showed αSMA-expressing FBs and high NGF levels. Advanced OCP-FBs showed higher αSMA expression associated with higher p75NTR and lower trkANGFR expression, as compared to early counterparts. αSMA 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 αSMA/p75NTR expression and TGFβ1/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.