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Published on: November 17, 2018
Lysyl oxidase-like 4 involvement in retinoic acid epithelial wound healing
Aurélie Comptour1, Marion Rouzaire1, Corinne Belville1,2
1Clermont Université, Université d'Auvergne, EA7281 - Retinoids, Reproduction Developmental Diseases, School of Medicine, F-63000 Clermont-Ferrand, France.
Abstract:
Vitamin A and its active forms (retinoic acids/RAs) are known to have pro-healing properties, but their mechanisms of action are still poorly understood. This work aimed to identify the cellular and molecular processes by which atRA (all-trans RA) improves wound healing, using an in vivo model of mouse corneal alkali burns and an in vitro cellular human corneal epithelial injury model. Regulation by atRA has been studied on most of the cellular events that occur in wound healing. We investigated the direct influence of atRA on a specific target gene known to be involved in the extracellular matrix (ECM) dynamics, one of the pathways contributing to epithelial repair. Our results demonstrate that atRA promotes corneal epithelial wound healing by acting preferentially on migration. The induction of lysyl oxidase-like 4 (LOXL4) expression by atRA in the corneal epithelium environment was established as essential in the mechanism of atRA-dependent wound healing. Our study describes for the first time a direct link between a retinoic-induced gene and protein, LOXL4, and its general clinical pro-healing properties in ECM dynamics.
Insights
All-trans retinoic acid (atRA) accelerates corneal wound healing by enhancing cell migration. This effect is mediated by the induction of lysyl oxidase-like 4 (LOXL4), a key gene in extracellular matrix dynamics.
Area of Science:
- Ophthalmology
- Cell Biology
- Biochemistry
Background:
- Vitamin A derivatives, particularly retinoic acids (RAs), are recognized for their potential to promote tissue repair.
- However, the precise molecular mechanisms underlying the pro-healing effects of RAs, especially all-trans retinoic acid (atRA), remain incompletely elucidated.
Purpose of the Study:
- To investigate the cellular and molecular pathways through which atRA enhances corneal wound healing.
- To identify specific target genes regulated by atRA that contribute to epithelial repair.
Main Methods:
- Utilized an in vivo mouse corneal alkali burn model and an in vitro human corneal epithelial cell injury model.
- Examined the direct impact of atRA on gene expression related to extracellular matrix (ECM) dynamics, focusing on epithelial repair processes.
Main Results:
- Demonstrated that atRA significantly promotes corneal epithelial wound healing, primarily by enhancing cell migration.
- Established that atRA induces the expression of lysyl oxidase-like 4 (LOXL4) in the corneal epithelium.
- Confirmed LOXL4 induction as a critical component of atRA-mediated wound healing.
Conclusions:
- All-trans retinoic acid (atRA) accelerates corneal epithelial wound healing through enhanced cell migration.
- The induction of lysyl oxidase-like 4 (LOXL4) by atRA is essential for its pro-healing effects.
- This study reveals a novel link between atRA, LOXL4 expression, and extracellular matrix remodeling in corneal repair.
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