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Jae Chan Kim, Soo Hyun Park, Kyoung Woo Kim; The role of insulin-like growth factor binding protein 2 (IGFBP2) in the corneal fibroblast differentiation. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5722. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Previously, we reported that keratocyte-conditioned medium (KCM) facilitates the differentiation of human mesenchymal stem cells (hMSCs) into corneal keratocyte-like cells. This study is designed to investigate the roles of insulin-like growth factor binding protein 2 (IGFBP2) for the regulation of corneal fibroblast differentiation as a newly unveiled component of KCM.
Immunodot blot analysis was performed to identify the factors that are highly secreted, especially in KCM. Then, we investigated whether IGFBP2 differentiates hMSCs into keratocyte-like cells and whether maintains the phenotypes of keratocyte in human corneal fibroblasts (HCFs) by analyzing expression patterns of alpha-smooth muscle actin (α-SMA) and keratocyte markers including keratocan, lumican and aldehyde dehydrogenase 1 family member A1 (ALDH1A1). Furthermore, to specify the role of IGFBP2, the expression of α-SMA and keratocyte markers was determined in transforming growth factor beta 1 (TGFβ1)-induced corneal myofibroblast and in HCFs after knockdown of IGFBP2.
The most prominent factor in both KCM and amniotic membrane extract was IGFBP2. IGFBP2 increased the expression of IGFBP2, keratocan and ALDH1A1, and decreased α-SMA expression in hMSCs and HCFs. IGFBP2 inhibited TGFβ1-induced up-regulation of α-SMA and increased expressions of keratocan and ALDH1A1 in HCFs. Furthermore, the knockdown of IGFBP2 increased α-SMA expression and decreased ALDH1A1 level in HCFs.
IGFBP2 is strongly associated with restoration of keratocyte phenotype in HCFs. Our results show an important novel role of IGFBP2 in regulation of corneal fibroblast differentiation and suggest that IGFBP2 can be a therapeutic candidate for corneal anti-fibrotic strategy.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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