Lysyl oxidase-like 4 involvement in retinoic acid epithelial wound healing.
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.
Clermont Université, Université d'Auvergne, EA7281 - Retinoids, Reproduction Developmental Diseases, School of Medicine, F-63000 Clermont-Ferrand, France.
Aurélie
A
Comptour
Clermont Université, Université d'Auvergne, EA7281 - Retinoids, Reproduction Developmental Diseases, School of Medicine, F-63000 Clermont-Ferrand, France.
Marion
M
Rouzaire
Clermont Université, Université d'Auvergne, EA7281 - Retinoids, Reproduction Developmental Diseases, School of Medicine, F-63000 Clermont-Ferrand, France.|Clermont Université, Université d'Auvergne, GReD, F-63000 Clermont-Ferrand, France.
Corinne
C
Belville
Clermont Université, Université d'Auvergne, EA7281 - Retinoids, Reproduction Developmental Diseases, School of Medicine, F-63000 Clermont-Ferrand, France.|CHU Clermont-Ferrand, Ophthalmology Department, F-63000 Clermont-Ferrand, France.
Nicolas
N
Bonnin
Clermont Université, Université d'Auvergne, EA7281 - Retinoids, Reproduction Developmental Diseases, School of Medicine, F-63000 Clermont-Ferrand, France.|CHU Clermont-Ferrand, Ophthalmology Department, F-63000 Clermont-Ferrand, France.
Estelle
E
Daniel
Clermont Université, Université d'Auvergne, EA7281 - Retinoids, Reproduction Developmental Diseases, School of Medicine, F-63000 Clermont-Ferrand, France.|CHU Clermont-Ferrand, Ophthalmology Department, F-63000 Clermont-Ferrand, France.
Frédéric
F
Chiambaretta
Clermont Université, Université d'Auvergne, EA7281 - Retinoids, Reproduction Developmental Diseases, School of Medicine, F-63000 Clermont-Ferrand, France.
Loïc
L
Blanchon
Clermont Université, Université d'Auvergne, EA7281 - Retinoids, Reproduction Developmental Diseases, School of Medicine, F-63000 Clermont-Ferrand, France.
Vincent
V
Sapin
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D019573:Epithelium, Corneal / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D051379:Mice; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014212:Tretinoin / Q000494:pharmacology*; D014945:Wound Healing
D014212:Tretinoin; D008249:Protein-Lysine 6-Oxidase