Transforming growth factor-β induces expression of vascular endothelial growth factor in human retinal pigment epithelial cells:: Involvement of mitogen-activated protein kinases
Transforming growth factor-β induces expression of vascular endothelial growth factor in human retinal pigment epithelial cells:: Involvement of mitogen-activated protein kinases
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DOI：
10.1002/jcp.10378
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发表时间：
2003-12-01
影响因子：
5.6
通讯作者：
Hooks, JJ
中科院分区：
文献类型：
--
作者：
Nagineni, CN;Samuel, W;Hooks, JJ
血管内皮生长因子（VEGF）是脉络膜和视网膜新生血管形成的主要因子，与年龄相关性黄斑变性（AMD）和糖尿病视网膜病变相关。视网膜色素上皮（Retinal pigment epithelium，RPE）位于视网膜和脉络膜之间，在视网膜疾病中起关键作用。我们研究了各种生长因子对人视网膜色素上皮细胞培养物（HRPE）VEGF表达和分泌的影响。RT-PCR分析显示存在三种亚型的mRNA，分别对应于VEGF 121、165和189，它们被TGF-β 1上调。TGF-β 1、β 2和β 3是HRPE细胞分泌VEGF的有效诱导剂，而bFGF、PDGF、TGF-α和GMCSF则无作用。TGF-β受体11型抗体显著逆转TGF-β诱导的VEGF分泌。而TGF-β超家族成员activin、BMP 2和BMP对HRPE中VEGF的表达无影响。MAP激酶抑制剂SB 203580和U 0126显著抑制TGF-β诱导的VEGF mRNA水平和蛋白分泌，但分别不受staurosporine和PDTC、蛋白激酶C和NF-κ B通路抑制剂的抑制。TGF-β还诱导源自人眼脉络膜的成纤维细胞表达VEGF。TGF-β诱导RPE和脉络膜细胞分泌VEGF可能在AMD的脉络膜新生血管（CNV）中起重要作用。由于HRPE分泌VEGF受MAP激酶途径调节，因此MAP激酶抑制剂可能具有作为AMD中CNV治疗剂的潜在用途。2003.出版2003 Wiley-Liss，lnc.（匕首）。
Vascular endothelial growth factor (VEGF) is a major agent in choroidal and retinal neovascularization, events associated with age-related macular degeneration (AMD) and diabetic retinopathy. Retinal pigment epithelium (RPE), strategically located between retina and choroid, plays a critical role in retinal disorders. We have examined the effects of various growth factors on the expression and secretion of VEGF by human retinal pigment epithelial cell cultures (HRPE). RT-PCR analyses revealed the presence of three isoforms of mRNA corresponding to VEGF 121, 165, and 189 that were up regulated by TGF-beta1. TGF-beta1, beta2, and beta3 were the potent inducers of VEGF secretion by HRPE cells whereas bFGF, PDGF, TGF-alpha, and GMCSF had no effects. TGF-beta receptor type 11 antibody significantly reversed induction of VEGF secretion by TGF-beta. In contrast activin, inhibin and BMP, members of TGF-beta super family, had no effects on VEGF expression in HRPE. VEGF mRNA levels and protein secretion induced by TGF-beta were significantly inhibited by SB203580 and U0126, inhibitors of MAP kinases, but not by staurosporine and PDTC, protein kinase C and NF-kappaB pathway inhibitors, respectively. TGF-beta also induced VEGF expression by fibroblasts derived from human choroid of eye. TGF-beta induction of VEGF secretion by RPE and choroid cells may play a significant role in choroidal neovascularization (CNV) in AMD. Since the secretion of VEGF by HRPE is regulated by MAP kinase pathways, MAP kinase inhibitors may have potential use as therapeutic agents for CNV in AMD. 2003. Published 2003 Wiley-Liss, lnc.(dagger).