Molecular Basis for Keratoconus: Lack of TrkA Expression and Its Transcriptional Repression by Sp3

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2005 Nov 9

PMID 16275928

Citations 15

Authors

Alessandro Lambiase

Daniela Merlo

Cristiana Mollinari

Paolo Bonini

Anna Maria Rinaldi

Mauro D Amato

Alessandra Micera

Marco Coassin

Paolo Rama

Stefano Bonini

Enrico Garaci

Affiliations

Soon will be listed here.

Abstract

Keratoconus is the most common corneal dystrophy that leads to severe visual impairment. Although the major etiological factors are genetic, the pathogenetic mechanism(s) is unknown. No medical treatments exist, and the only therapeutic approach is corneal transplantation. Recent data demonstrate the involvement of nerve growth factor (NGF) in trophism and corneal wound healing. In this study, we investigated alterations in the NGF pathway in keratoconus-affected corneas and found a total absence of the NGF-receptor TrkA (TrkA(NGFR)) expression and a decreased expression of NGF and p75(NTR). The absence of TrkA(NGFR) expression was associated with a strong increase in the Sp3 repressor short isoform(s) and a lack of the Sp3 activator long isoform. Sp3 is a bifunctional transcription factor that has been reported to stimulate or repress the transcription of numerous genes. Indeed, we found that Sp3 short isoform(s) overexpression in cell culture results in a down-regulation of TrkA(NGFR) expression. We suggest that an imbalance in Sp transcription-factor isoforms may play a role in controlling the NGF signaling, thus contributing to the pathogenesis of keratoconus. This mechanism for the transcriptional repression of the TrkA(NGFR) gene can provide the platform for the development of a therapeutic strategy.

Citing Articles

Level of Secretion and the Role of the Nerve Growth Factor in Patients with Keratoconus before and after Collagen Fibre Cross-Linking Surgery.

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Systematically Displaying the Pathogenesis of Keratoconus Multi-Level Related Gene Enrichment-Based Review.

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Kriszt A, Losonczy G, Berta A, Takacs L Int J Ophthalmol. 2015; 8(5):922-7.

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