All-trans retinoic acid regulates the expression of the extracellular matrix protein fibulin-1 in the guinea pig sclera and human scleral fibroblasts

[摘要] Purpose: Fibulin-1 (FBLN1) mRNAis expressed in human sclera and is an important adhesion modulatoryprotein that can affect cell–matrix interactions and tissue remodeling.Scleral remodeling is influenced by all-trans retinoic acid (RA). Ourpurpose was to confirm the presence of fibulin-1 protein in guinea pigsclera and investigate the effect of RA on the expression of fibulin-1in guinea pig sclera in vivo and in cultured human scleral fibroblasts(HSFs). Methods: Confocal fluorescencemicroscopy was used to study fibulin-1 and aggrecan expression andlocalization in sclera from control guinea pigs and in animals given RAby daily gavage from 4 to 8 days of age. The effects of RA (from 10−9to 10−5 M) on fibulin-1 expression in HSFs were observed byimmunohistochemistry and assayed by real-time PCR and western blotanalysis. Results: Fibulin-1 protein expressionwas detected by confocal fluorescence microscopy in guinea pig scleraand in cultured HSFs. Upregulation of fibulin-1 in scleral tissue wasobserved after feeding with RA. In vitro, the level of Fbln1mRNA was increased after treatment of HSFs with RA (at concentrationsof 10−8 to 10−6 M; p<0.001), with a maximumeffect at 10−7 M. Fibulin-1 protein levels weresignificantly increased after treatment of HSFs with 10−7 Mof RA for 24 or 48 h (p<0.05). Conclusions: Fibulin-1 protein wasexpressed in guinea pig sclera and cultured HSFs. Expression wasregulated by RA, a molecule known to be involved in the regulation ofeye growth. Further studies on the role of fibulin-1 in the regulationof eye growth, including during the development of myopia, aretherefore warranted.

[学科分类] 生物化学/生物物理