In response to corneal injury, cytokines and growth factors play a crucial role by influencing epithelial-stromal interaction during the healing and reparative processes which may resolve in tissue remodeling and fibrosis. While transforming growth factor-beta1 (TGF-beta1) is considered the main profibrogenic modulator of these process, recently the nerve growth factor (NGF) appears as a pleiotropic modulator of wound-healing and inflammatory responses. Interestingly in the cornea, where NGF, trkA(NGFR) and p75(NTR) are expressed by epithelial cells and keratocytes, the NGF eye-drop induces the healing of neurotrophic or autoimmune corneal ulcers. During corneal healing, quiescent keratocytes are replaced by active fibroblast-like keratocytes/myofibroblasts. While the NGF effect on epithelial cells has been investigated, no data are reported for NGF effects on fibroblastic-keratocytes, during corneal healing. NGF, trkA(NGFR) and p75(NTR) were found expressed by fibroblastic-keratocytes. NGF was able to induce fibroblastic-keratocyte differentiation into myofibroblasts, migration, Metalloproteinase-9 expression/activity and contraction of a 3D collagen gel, without affecting their proliferation and collagen production. These data also show a two-directional control of fibroblastic-keratocytes by NGF and TGF-beta1. To sum up, the findings of this study indicate that NGF can modulate some functional activities of fibroblastic-keratocytes, thus substantiating the healing effects of NGF on corneal wound-healing.

Nerve growth factor effect on human primary fibroblastic-keratocytes: possible mechanism during corneal healing / Micera, Alessandra; Lambiase, Alessandro; Puxeddu, Ilaria; Aloe, Luigi; Stampachiacchiere, Barbara; Levi Schaffer, Francesca; Bonini, Sergio; Bonini, Stefano. - In: EXPERIMENTAL EYE RESEARCH. - ISSN 0014-4835. - STAMPA. - 83:4(2006), pp. 747-757. [10.1016/j.exer.2006.03.010]

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

LAMBIASE, ALESSANDRO;
2006

Abstract

In response to corneal injury, cytokines and growth factors play a crucial role by influencing epithelial-stromal interaction during the healing and reparative processes which may resolve in tissue remodeling and fibrosis. While transforming growth factor-beta1 (TGF-beta1) is considered the main profibrogenic modulator of these process, recently the nerve growth factor (NGF) appears as a pleiotropic modulator of wound-healing and inflammatory responses. Interestingly in the cornea, where NGF, trkA(NGFR) and p75(NTR) are expressed by epithelial cells and keratocytes, the NGF eye-drop induces the healing of neurotrophic or autoimmune corneal ulcers. During corneal healing, quiescent keratocytes are replaced by active fibroblast-like keratocytes/myofibroblasts. While the NGF effect on epithelial cells has been investigated, no data are reported for NGF effects on fibroblastic-keratocytes, during corneal healing. NGF, trkA(NGFR) and p75(NTR) were found expressed by fibroblastic-keratocytes. NGF was able to induce fibroblastic-keratocyte differentiation into myofibroblasts, migration, Metalloproteinase-9 expression/activity and contraction of a 3D collagen gel, without affecting their proliferation and collagen production. These data also show a two-directional control of fibroblastic-keratocytes by NGF and TGF-beta1. To sum up, the findings of this study indicate that NGF can modulate some functional activities of fibroblastic-keratocytes, thus substantiating the healing effects of NGF on corneal wound-healing.
2006
Cell Differentiation; Cell Movement; Cell Proliferation; Cells, Cultured; Cornea; Dose-Response Relationship, Drug; Fibroblasts; Humans; Nerve Growth Factor; Receptor, Nerve Growth Factor; Receptor, trkA; Reverse Transcriptase Polymerase Chain Reaction; Wound Healing
01 Pubblicazione su rivista::01a Articolo in rivista
Nerve growth factor effect on human primary fibroblastic-keratocytes: possible mechanism during corneal healing / Micera, Alessandra; Lambiase, Alessandro; Puxeddu, Ilaria; Aloe, Luigi; Stampachiacchiere, Barbara; Levi Schaffer, Francesca; Bonini, Sergio; Bonini, Stefano. - In: EXPERIMENTAL EYE RESEARCH. - ISSN 0014-4835. - STAMPA. - 83:4(2006), pp. 747-757. [10.1016/j.exer.2006.03.010]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/793314
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