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Nerve growth factor has a modulatory role on human primary fibroblast cultures derived from vernal keratoconjunctivitis-affected conjunctiva.

ABSTRACT: PURPOSE: To evaluate the role of nerve growth factor (NGF) in remodeling processes of vernal keratoconjunctivitis (VKC). VKC is a chronic inflammatory disorder of the conjunctiva and is characterized by marked tissue remodeling. NGF, a pleiotrophic factor with documented profibrogenic activities, is produced by inflammatory and structural cells populating the VKC conjunctiva and is increased in the serum and tears of VKC patients. METHODS: Primary cultures of VKC-derived fibroblasts (VKC-FBs) were exposed to increasing NGF concentrations (1-500 ng/ml) to evaluate and compare the expression of alpha-smooth muscle actin (alphaSMA, a defining myofibroblast marker), collagens (types I and IV), and metalloproteinases and tissue inhibitors (MMP9/TIMP1, MMP2/TIMP2) at the biochemical as well as molecular levels. RESULTS: Endogenous NGF was increased in the VKC-FB supernatant, as compared to healthy-FB supernatant. VKC-FBs expressed alphaSMA and increased types I and IV collagens. VKC-FBs, and in particular all alphaSMA positive cells, expressed both trkA(NGFR) and p75(NTR), while healthy-FBs only expressed trkA(NGFR). Exogenous NGF did not change alphaSMA expression, while alphaSMA expression was enhanced by specific neutralization of p75(NTR). NGF (10 ng/ml) exposure significantly decreased type I collagen expression, without affecting type IV collagen, and increased MMP9mRNA and protein. CONCLUSIONS: The autocrine modulation of differentiation and response of VKC-FBs to NGF exposure with downregulation of type I collagen and upregulation of MMP9 expression supports a relevant role for NGF in tissue remodeling of VKC.

SUBMITTER: Micera A

PROVIDER: S-EPMC2774460 | biostudies-literature | 2007

REPOSITORIES: biostudies-literature

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Nerve growth factor has a modulatory role on human primary fibroblast cultures derived from vernal keratoconjunctivitis-affected conjunctiva.

Micera Alessandra A Lambiase Alessandro A Stampachiacchiere Barbara B Sgrulletta Roberto R Normando Eduardo Maria EM Bonini Sergio S Bonini Stefano S

Molecular vision 20070621

<h4>Purpose</h4>To evaluate the role of nerve growth factor (NGF) in remodeling processes of vernal keratoconjunctivitis (VKC). VKC is a chronic inflammatory disorder of the conjunctiva and is characterized by marked tissue remodeling. NGF, a pleiotrophic factor with documented profibrogenic activities, is produced by inflammatory and structural cells populating the VKC conjunctiva and is increased in the serum and tears of VKC patients.<h4>Methods</h4>Primary cultures of VKC-derived fibroblasts ...[more]

PMID: 17653039

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Project description:Sjögren syndrome (SS) is an autoimmune condition that targets the salivary and lacrimal glands, with cardinal clinical signs of dry eye (keratoconjunctivitis sicca, KCS) and dry mouth. The conjunctiva of SS patients is often infiltrated by immune cells that participate in the induction and maintenance of local inflammation. The purpose of this study was to investigate immune-related molecular pathways activated in the conjunctiva of SS patients. Female SS patients (n=7) and controls (n=19) completed a series of oral, ocular surface exams. Symptom severity scores were evaluated using validated questionnaires (OSDI and SANDE). All patients fulfilled the ACR/EULAR criteria for SS and the criteria for KCS. Fluorescein and lissamine green dye staining evaluated tear-break-up time (TBUT), corneal and conjunctival disease, respectively. Impression cytology of the temporal bulbar conjunctiva was performed to collect cells lysed and subjected to gene expression analysis using the NanoString Immunology Panel. 53/594 differentially expressed genes (DEGs) were observed between SS and healthy controls; 49 DEGs were upregulated, and 4 were downregulated (TRAF5, TGFBI, KLRAP1, and CMKLRI). The top 10 DEGs in descending order were BST2, IFITM1, LAMP3, CXCL1, IL19, CFB, LY96, MX1, IL4R, CDKN1A. Twenty pathways had a global significance score greater or equal to 2. Spearman correlations showed that 29/49 upregulated DEGs correlated with either TBUT (inverse) or OSDI or conjunctival staining score (positive correlations). Venn diagrams identified that 26/29 DEGs correlated with TBUT, 5/26 DEGs correlated with OSDI, and 16/26 correlated with conjunctival staining scores. Five upregulated DEGs (CFB, CFI, IL1R1, IL2RG, IL4R) were uniquely negatively correlated with TBUT. These data indicate that the conjunctiva of SS patients exhibits a phenotype of immune activation, although some genes could be inhibitory. Some of the DEGs and pathways overlap with previous DEGs in salivary gland biopsies, but new DEGs were identified, and some of these correlated with symptoms and signs of dry eye. Our results indicate that gene analysis of conjunctiva imprints is a powerful tool to understand the pathogenesis of SS and develop new therapeutic targets.

Project description:IntroductionVernal keratoconjunctivitis is a chronic bilateral severe form of allergic conjunctivitis which affects normal activities in school/work. It is a severe form of allergies in warm and dry tropical and sub-tropical countries. Its prevalence in Ethiopia ranges from 5.2% to7.3%. Most studies are institution based and do not address specific factors associated with vernal keratoconjunctivitis. There is no a study that shows the magnitude of vernal keratoconjunctivitis in the study area.ObjectiveTo assess the prevalence of vernal keratoconjunctivitis and its associated factors among children in Gambella town, Southwest Ethiopia, 2018.Methods and materialsA community based cross-sectional study was conducted from April 25 to May 12, 2018, in Gambella town. A total of 578 study participants were selected using a systematic random sampling technique. A pre-tested semi-structured questionnaire, torch, and magnifying loop were used to collect data. The data was entered into epidemiological information 7.1 and exported to statistical package for social science for analysis. Binary logistic regression analysis model was fitted to identify factors associated with vernal keratoconjunctivitis. Odds ratio with respected 95% CI was used to identify the direction and strength of association.ResultsA total of 574 children participated in this study representing a response rate of 99.30%. The mean age of the participants was 9.74±4.0 years. The prevalence of vernal keratoconjunctivitis was 11.10% (95% CI: 8.70, 13.90). Male sex (adjusted odds ratio = 4.12(95% CI: 1.42, 11.91)), close animal contact (adjusted odds ratio = 3.45(95% CI: 1.14, 10.41)), dust exposure (adjusted odds ratio = 3.38(95% CI: 1.31, 10.04)), and personal systemic allergy history (adjusted odds ratio = 4.82(1.40, 16.72) were independently associated with vernal keratoconjunctivitis.ConclusionThe prevalence of VKC was high among children in Gambella town. Sex being male, close animal contact, personal systemic allergy history, and dust exposure were positively associated with vernal keratoconjunctivitis independently.

Dataset Information

Nerve growth factor has a modulatory role on human primary fibroblast cultures derived from vernal keratoconjunctivitis-affected conjunctiva.

Publications

Nerve growth factor has a modulatory role on human primary fibroblast cultures derived from vernal keratoconjunctivitis-affected conjunctiva.

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