Discrete expression and distribution pattern of TIMP-3 in the human retina and choroid.
Discrete expression and distribution pattern of TIMP-3 in the human retina and choroid.
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TIMP-3 在人视网膜和脉络膜中的离散表达和分布模式。
DOI：
10.1076/ceyr.16.2.102.5086
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发表时间：
1997
影响因子：
2
通讯作者：
Acott,TS
中科院分区：
文献类型：
--
作者：
Vranka,JA;Johnson,E;Zhu,X;Shepardson,A;Alexander,JP;Bradley,JM;Wirtz,MK;Weleber,RG;Klein,ML;Acott,TS
PURPOSE细胞外基质动态平衡部分依赖于一系列基质金属蛋白酶及其特定的抑制物，金属蛋白酶的组织抑制物(TIMPs)。最近，在几个索尔斯比氏眼底营养不良(SFD)家系的患者中发现了TIMP-3基因缺陷。关于TIMP-3的功能，甚至其在视网膜或脉络膜中的存在，目前还知之甚少。方法我们利用逆转录-聚合酶链式反应和Northern分析来评估TIMP mRNA的表达，并用免疫印迹法来评估选定的人视网膜和脉络膜细胞产生的TIMP蛋白。结果在培养的人视网膜色素上皮(RPE)、脉络膜微血管内皮细胞和周细胞中发现了TIMP-3的转录本。RPE细胞也表达和分泌TIMP-3蛋白，TIMP-3蛋白定位于细胞外基质，在培养上清液中不存在；TIMP-1和TIMP-2几乎仅在培养液中存在。人视网膜/脉络膜切片免疫组织化学染色显示TIMP-3在Bruch膜，特别是靠近RPE表面和内皮细胞的表面，可能在它们的基底膜，在视网膜的其他部分染色很少。结论TIMP-1、TIMP-2和TIMP-3在视网膜和脉络膜中有不同的表达模式。这种分布和表达模式部分解释了为什么TIMP-3突变导致SFD，而不是其他视网膜病变，如与增殖性糖尿病视网膜病变相关的病变。
PURPOSEExtracellular matrix homeostasis is dependent in part upon a family of matrix metalloproteinases and their specific inhibitors, the tissue inhibitors of metalloproteinases (TIMPs). Recently, gene defects in TIMP-3 have been identified in the affected individuals of several families with Sorsby's fundus dystrophy (SFD). Very little information is available regarding TIMP-3 function or even its existence in the retina or choroid.METHODSWe used reverse transcription-polymerase chain reaction and Northern analysis to evaluate the expression of TIMP mRNA and Western immunoblots to evaluate TIMP protein produced by select cells of the human retina and choroid. We also used these methods and immunohistochemistry to localize the TIMPs in the retina and choroid.RESULTSTIMP-3 transcripts are found in cultured human retinal pigment epithelium (RPE), choroidal microcapillary endothelium and pericytes. RPE cells also express and secrete TIMP-3 protein, which is localized to the extracellular matrix and is not found in culture medium; TIMP-1 and -2 are found almost exclusively in the medium. Immunohistochemistry of human retina/ choroid sections shows pronounced TIMP-3 immunostaining in Bruch's membrane, particularly near the surface of the RPE and endothelial cells, presumably in their basement membranes, with minimal staining in other portions of the retina. Immunostaining for TIMP-1 is absent and for TIMP-2 is much less prevalent, but detectable in Bruch's membrane.CONCLUSIONSTIMP-1, -2 and -3 exhibit distinctive expression patterns in the retina and choroid. This distribution and expression pattern partially explains why TIMP-3 mutations result in SFD, rather than other retinal pathologies, such as those associated with proliferative diabetic retinopathy.
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DOI：
10.1016/s0021-9258(17)37115-6
发表时间：
1994-03
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
K. Leco;R. Khokha;N. Pavloff;S. Hawkes;D. Edwards
通讯作者：
K. Leco;R. Khokha;N. Pavloff;S. Hawkes;D. Edwards
人类组织金属蛋白酶抑制剂 (TIMP) 基因家族的一个新成员在 G1 进展、有丝分裂刺激、分化和衰老过程中受到调节。
影响因子：
4.8
作者：
M. Wick;C. Bürger;S. Brüsselbach;Lucibello Fc;R. Müller
通讯作者：
R. Müller
影响因子：
4.4
作者：
J. Alexander;J. Samples;E. Michael;Van Duskirk;Ted Acotr
通讯作者：
J. Alexander;J. Samples;E. Michael;Van Duskirk;Ted Acotr
影响因子：
4.4
作者：
J. Samples;J. Alexander;T. Acott
通讯作者：
J. Samples;J. Alexander;T. Acott
通过核磁共振波谱解析生理相关蛋白质的溶液结构。
影响因子：
18.2
作者：
N. Mackenzie;P. Gooley;L. A. Hardaway
通讯作者：
L. A. Hardaway