All-trans retinoic acid regulates the expression of the extracellular matrix protein fibulin-1 in the guinea pig sclera and human scleral fibroblasts
نویسندگان
چکیده
PURPOSE Fibulin-1 (FBLN1) mRNA is expressed in human sclera and is an important adhesion modulatory protein that can affect cell-matrix interactions and tissue remodeling. Scleral remodeling is influenced by all-trans retinoic acid (RA). Our purpose was to confirm the presence of fibulin-1 protein in guinea pig sclera and investigate the effect of RA on the expression of fibulin-1 in guinea pig sclera in vivo and in cultured human scleral fibroblasts (HSFs). METHODS Confocal fluorescence microscopy was used to study fibulin-1 and aggrecan expression and localization in sclera from control guinea pigs and in animals given RA by daily gavage from 4 to 8 days of age. The effects of RA (from 10(-9) to 10(-5) M) on fibulin-1 expression in HSFs were observed by immunohistochemistry and assayed by real-time PCR and western blot analysis. RESULTS Fibulin-1 protein expression was detected by confocal fluorescence microscopy in guinea pig sclera and in cultured HSFs. Upregulation of fibulin-1 in scleral tissue was observed after feeding with RA. In vitro, the level of Fbln1 mRNA was increased after treatment of HSFs with RA (at concentrations of 10(-8) to 10(-6) M; p<0.001), with a maximum effect at 10(-7) M. Fibulin-1 protein levels were significantly increased after treatment of HSFs with 10(-7) M of RA for 24 or 48 h (p<0.05). CONCLUSIONS Fibulin-1 protein was expressed in guinea pig sclera and cultured HSFs. Expression was regulated by RA, a molecule known to be involved in the regulation of eye growth. Further studies on the role of fibulin-1 in the regulation of eye growth, including during the development of myopia, are therefore warranted.
منابع مشابه
All-trans Retinoic Acid Regulates the Balance of Treg-Th17 Cells through ERK and P38 Signaling Pathway
متن کامل
All-trans retinoic acid modulates mitogen-activated protein kinase pathway activation in human scleral fibroblasts through retinoic acid receptor beta
PURPOSE All-trans retinoic acid (ATRA) is known to inhibit the proliferation of human scleral fibroblasts (HSFs) and to modulate the scleral intercellular matrix composition, and may therefore serve as a mediator for controlling eye growth. Cell proliferation is regulated by the mitogen-activated protein kinase (MAPK) pathway. The aim of the current study was to investigate whether changed acti...
متن کاملIdentification of genes expressed in a human scleral cDNA library.
PURPOSE Clones established from a human scleral cDNA library were systematically sequenced. Public database sequence comparisons were performed to generate a profile of genes expressed in the human sclera and identify candidate genes for inherited diseases with scleral involvement. METHODS A directionally cloned pCMV-PCR cDNA library was constructed from RNA isolated from scleras of human don...
متن کاملRole of bone morphogenetic proteins in form-deprivation myopia sclera
PURPOSE To clarify the role of bone morphogenetic proteins (BMP-2,-4,-5) in sclera remodeling during myopia induction and their effect on sclera fibroblasts in cell culture. METHODS Reverse transcription and polymerase chain reaction (RT-PCR) as well as immunofluorescence were used to detect the expression of the BMPs in human and guinea pig posterior sclera. In guinea pig form-deprivation my...
متن کاملThe effect of bilateral intrahippocampal injection of all–trans retinoic acid on spatial learning in adult male rats.
Introduction: Previous studies have shown that vitamin A and its derivatives such as retinoid and all-trans retinoic acid have a crucial role in memory, learning and synaptic plasticity. The receptors of vitamin A are seen in different parts of the brain such as hippocampus, where vitamin A has an important role in learning. In this study, the effect of intrahippocampal (CA1) injection of al...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 16 شماره
صفحات -
تاریخ انتشار 2010