Nerve growth factor effect on human primary fibroblastic-keratocytes: Possible mechanism during corneal healing

Micera, Alessandra; Lambìase, Alessandro; Puxeddu, Ilaria; Aloe, Luigi; Stampachiacchiere, Barbara; Levi‐Schaffer, Francesca; Bonini, Sergio; Bombardieri, Stefano

doi:10.1016/j.exer.2006.03.010

Cited by 63 publications

(48 citation statements)

References 33 publications

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“…[27][28][29][30][31][32][33][34][35][36] In addition, we tested the in vitro effects of NGF using Telomerase-immortalized HCLEs in contrast to previous works concentrated on the effect of NGF on corneal fibroblasts and conjunctiva epithelial cells. 46,47,53 Epithelial resurfacing occurred significantly faster in corneas treated with NGF compared with controls (P < 0.01). Furthermore, epithelial proliferation increased significantly in NGF-treated corneas (P < 0.01).…”

Section: Discussionmentioning

confidence: 98%

“…These results agree with previous works showing upregulation of TrkA expression in response to NGF. 46,47,53 During corneal epithelial resurfacing, cells migrating to cover the wound area drastically reduce proliferative activity. However, cells distal to the original wound exhibit a greatly enhanced level of proliferative activity.…”

Section: Discussionmentioning

confidence: 99%

“…45 Assuming that NGF induces MMP-9 expression 46 by activating the TrkA receptor, 47,48 we wondered if the cell spreading observed in our experiment in response to NGF was MMP-9 mediated. Cross-sections revealed predominant expression in the epithelium within the wounded area (Fig.…”

Section: Mmp-9 Is Briefly Upregulated In Response To Exogenous Ngfmentioning

confidence: 99%

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Nerve Growth Factor Promotes Corneal Epithelial Migration by Enhancing Expression of Matrix Metalloprotease-9

Blanco–Mezquita

Martínez‐García

Proença

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Nerve growth factor (NGF) is a neuropeptide essential for the development, survival, growth, and differentiation of corneal cells. Its effects are mediated by both TrkA and p75 receptors. Clinically relevant use of NGF was introduced to treat neurotrophic ulcerations in patients. Herein, we examine the mechanisms by which NGF enhances epithelial wound healing both in vivo and in vitro.METHODS. An animal model using adult hens was implemented for the in vivo experiments. Laser ablation keratectomy was performed and animals were observed for up to 7 days. Epithelial healing was measured with fluorescein. In addition, proliferation was measured using BrdU incorporation and both TrkA and matrix metalloprotease-9 (MMP-9) expression were measured by immunohistochemistry (IHC) and Western blot (WB). In vitro experiments were carried out with telomerase-immortalized human corneal epithelial cells (HCLE). The rate of proliferation was measured using a colorimetric assay and BrdU incorporation. Realtime migration was evaluated with an inverted microscope. MMP-9 expression was evaluated by immunocytochemistry (ICC), WB, zymography, and RT-PCR. Finally, beta-4 integrin (b4) expression was assessed by ICC and WB.RESULTS. Faster epithelial healing was observed in NGF-treated corneas compared with controls (P < 0.01). These corneas showed increased proliferation, TrkA upregulation, and enhanced MMP-9 presence (P < 0.01). In vitro, faster spreading and migration were observed in response to NGF (P < 0.01). Enhanced proliferation, as well as enhanced TrkA and MMP-9 expression, and decreased b4 levels were observed after adding NGF (P < 0.01).CONCLUSIONS. NGF plays a major role during the epithelial healing process by promoting migration, a process that is accelerated by cell spreading. This effect is mediated by both the upregulation of MMP-9 and cleavage of b4 integrin.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

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Nerve Growth Factor Promotes Corneal Epithelial Migration by Enhancing Expression of Matrix Metalloprotease-9

Blanco–Mezquita

Martínez‐García

Proença

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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“…All 3 factors have, in fact, been shown to be expressed by the rat lacrimal gland tissue [121,122] in vivo, and in vitro it has been shown that conjunctival cells (epithelial cells, goblet cells, immune cells and fibroblasts) all produce, store, release, and utilize NGF. The diverse activity of NGF appears to modulate the activity of these cells, and therefore affect the secretion of cytokines and other growth factors [123][124][125] . Due to its wide-ranging effects, NGF is believed to be implicated in a variety of ocular diseases [126] .…”

Section: Preserved Retinal Function By Neurotrophic Factorsmentioning

confidence: 99%

What can we learn about stroke from retinal ischemia models?

D'Onofrio

Koeberle

2012

Acta Pharmacol Sin

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Retinal ischemia is a very useful model to study the impact of various cell death pathways, such as apoptosis and necrosis, in the ischemic retina. However, it is important to note that the retina is formed as an outpouching of the diencephalon and is part of the central nervous system. As such, the cell death pathways initiated in response to ischemic damage in the retina reflect those found in other areas of the central nervous system undergoing similar trauma. The retina is also more accessible than other areas of the central nervous system, thus making it a simpler model to work with and study. By utilizing the retinal model, we can greatly increase our knowledge of the cell death processes initiated by ischemia which lead to degeneration in the central nervous system. This paper examines work that has been done so far to characterize various aspects of cell death in the retinal ischemia model, such as various pathways which are activated, and the role neurotrophic factors, and discusses how these are relevant to the treatment of ischemic damage in both the retina and the greater central nervous system.

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“…Findings revealed increased baseline fibroblast proliferation in NGFR KO fibroblasts, but decreased responsiveness to exogenous NGF. The expression of NGF, NGFR, and trkA receptor has been demonstrated in human dermal fibroblasts and myofibroblasts [111], human lung fibroblasts [112], and primary human fibroblastic-keratocytes [113]. In the present study, fibroblasts from WT mice were stimulated to proliferate more when treated with NGF, but fibroblasts from NGFR KO mice were not responsive.…”

Section: Ngfb and Col1a1 Gene Expression In Isolated Primary Lung Fibmentioning

confidence: 52%

Repair of the airway epithelium after chlorine-induced injury.

Musah¹

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Nerve growth factor effect on human primary fibroblastic-keratocytes: Possible mechanism during corneal healing

Cited by 63 publications

References 33 publications

Nerve Growth Factor Promotes Corneal Epithelial Migration by Enhancing Expression of Matrix Metalloprotease-9

Nerve Growth Factor Promotes Corneal Epithelial Migration by Enhancing Expression of Matrix Metalloprotease-9

What can we learn about stroke from retinal ischemia models?

Repair of the airway epithelium after chlorine-induced injury.

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