Functional Characteristics of Connective Tissue Growth Factor on Vitreoretinal Cells

Functional Characteristics of Connective Tissue Growth Factor on Vitreoretinal Cells
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DOI:
10.2337/db06-1644
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发表时间:
2007-05
期刊:
影响因子:
7.7
通讯作者:
T. Kita;Y. Hata;M. Miura;Shuhei Kawahara;S. Nakao;T. Ishibashi
T. Kita;Y. Hata;M. Miura;Shuhei Kawahara;S. Nakao;T. Ishibashi
中科院分区:
医学1区
文献类型:
--
作者:
T. Kita;Y. Hata;M. Miura;Shuhei Kawahara;S. Nakao;T. Ishibashi

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结缔组织生长因子(CTGF)在增殖性玻璃体视网膜病变(如增殖性糖尿病视网膜病变和增殖性玻璃体视网膜病变(PVR))中的表达水平升高,但其在玻璃体视网膜细胞中的功能特点尚不清楚。在这项研究中,我们证明了CTGF对培养的透明细胞和牛视网膜色素上皮细胞(BRPEs)的生长促进作用,诱导p44/p42丝裂原活化蛋白激酶磷酸化和[3 H]胸苷掺入。CTGF还刺激了透明细胞和BRPEs合成纤维连接蛋白,但对这些细胞的胶原凝胶收缩没有显着影响。另一方面,CTGF对血管内皮细胞的增殖、迁移或体外管腔形成没有直接影响。然而,CTGF促进透明细胞和BRPE的血管内皮生长因子(VEGF)基因表达。虽然CTGF和VEGF在患有增生性玻璃体视网膜疾病的人玻璃体样本中的浓度升高,但这些浓度之间没有显著相关性。这些发现表明,CTGF似乎参与增殖膜的形成,而不直接调节其瘢痕收缩的增殖性玻璃体视网膜疾病的发病机制。尽管CTGF可能对视网膜新生血管形成没有直接作用或作用极小(如果有的话),但CTGF可能通过调节VEGF的表达而具有间接作用。
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 [3H]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.