Journal Article

Functional Characteristics of Connective Tissue Growth Factor on Vitreoretinal Cells

Takeshi Kita, Shuhei Kawahara, Yasuaki Hata, Muneki Miura, Shintaro Nakao, Tatsuro Ishibashi

2007

Overview

Functional Characteristics of Connective Tissue Growth Factor on Vitreoretinal Cells Takeshi Kita , Yasuaki Hata , Muneki Miura , Shuhei Kawahara , Shintaro Nakao and Tatsuro Ishibashi From the Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan Address correspondence and reprint requests to Yasuaki Hata, MD, PhD, Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan. E-mail: hatachan{at}med.kyushu-u.ac.jp Abstract Connective tissue growth factor (CTGF) level is elevated in eyes with proliferative vitreoretinal diseases, such as proliferative diabetic retinopathy and proliferative vitreoretinopathy (PVR), as we previously reported, but its functional characteristics on vitreoretinal cells are yet to be clarified. In this study, we demonstrated a growth-promoting effect of CTGF on cultured hyalocytes and bovine retinal pigment epithelial cells (BRPEs) with the induction of p44/p42 mitogen-activated protein kinase phosphorylation and [ 3 H]thymidine incorporation. CTGF also stimulated the synthesis of fibronectin by hyalocytes and BRPEs without significant effect on collagen gel contraction by these cells. On the other hand, CTGF had no direct effects on the proliferation, migration, or in vitro tube formation by vascular endothelial cells. Nevertheless, CTGF promoted vascular endothelial growth factor (VEGF) gene expression by hyalocytes and BRPEs. Although the concentrations of both CTGF and VEGF in the human vitreous samples with proliferative vitreoretinal diseases were elevated, there was no significant correlation between these concentrations. These findings indicate that CTGF appears to be involved in the formation of proliferative membranes without direct regulation of their cicatricial contraction in the pathogenesis of proliferative vitreoretinal diseases. Whereas CTGF might have no direct effects or minimal effects, if any, on retinal neovascularization, it is possible that CTGF has indirect effects by modulating the expression of VEGF. BAEC, bovine aortic endothelial cell BREC, bovine retinal capillary endothelial cell BRPE, bovine retinal pigment epithelial cell CTGF, connective tissue growth factor DMEM, Dulbecco's modified Eagle's medium FBS, fetal bovine serum HUVEC, human umbilical vein endothelial cell MAPK, mitogen-activated protein kinase PDR, proliferative diabetic retinopathy PVR, proliferative vitreoretinopathy REC, retinal capillary endothelial cell RPE, retinal pigment epithelial cell RRD, rhegmatogenous retinal detachment TGF-β, transforming growth factor-β VEGF, vascular endothelial growth factor Footnotes Published ahead of print at http://diabetes.diabetesjournals.org on 15 February 2007. DOI: 10.2337/db06-1644. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted February 5, 2007. Received November 23, 2006. DIABETES

• Publisher: American Diabetes Association
• Subject: Angiogenesis / Animals / Antibodies / Biological and medical sciences / Capillaries - drug effects / Capillaries - physiology / Care and treatment / Cattle / Cell Line / Cells / Cells, Cultured / Collagen / Collagen - metabolism / Complications and side effects / Connective tissue / Connective Tissue Growth Factor / Development and progression / Diabetes / Diabetes. Impaired glucose tolerance / Diabetic retinopathy / Diagnosis / DNA - biosynthesis / Endocrine pancreas. Apud cells (diseases) / Endocrinopathies / Etiopathogenesis. Screening. Investigations. Target tissue resistance / Extracellular matrix / Growth factors / Health aspects / Humans / Immediate-Early Proteins - pharmacology / Intercellular Signaling Peptides and Proteins - pharmacology / Kinases / Medical sciences / Membranes / Mitogen-Activated Protein Kinase 1 - drug effects / Mitogen-Activated Protein Kinase 1 - metabolism / Mitogen-Activated Protein Kinase 3 - drug effects / Mitogen-Activated Protein Kinase 3 - metabolism / Neovascularization, Physiologic / Pathogenesis / Phosphorylation / Proliferative vitreoretinopathy / Properties / Proteins / Recombinant Proteins - pharmacology / Retinal detachment / Thymidine - metabolism / Umbilical Veins / Vascular endothelial growth factor / Vitreous Body - drug effects / Vitreous Body - injuries / Vitreous Body - physiology / Wound Healing - drug effects