α1(IV)、α5(IV)和α6(IV)胶原链在正常成人及胎儿组织以及X连锁遗传性肾炎患者肾脏中的比较分布。

Comparative distribution of the alpha 1(IV), alpha 5(IV), and alpha 6(IV) collagen chains in normal human adult and fetal tissues and in kidneys from X-linked Alport syndrome patients.

作者信息

Peissel B, Geng L, Kalluri R, Kashtan C, Rennke H G, Gallo G R, Yoshioka K, Sun M J, Hudson B G, Neilson E G

机构信息

Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.

出版信息

J Clin Invest. 1995 Oct;96(4):1948-57. doi: 10.1172/JCI118241.

We have shown previously that the 5' ends of the genes for the alpha 5(IV) and alpha 6(IV) collagen chains lie head-to-head on Xq22 and are deleted in patients with Alport syndrome (AS)-associated diffuse leiomyomatosis. In this study, we raised a rabbit anti-human alpha 6(IV)chain antibody, demonstrated its specificity by the analysis of recombinant NC1 domains af all six type IV chains, and studied the distribution of the alpha 6(IV) chain in relation to the alpha 1(IV) and alpha 5(IV) chains in human adult and fetal tissues involved in AS and diffuse leiomyomatosis. The alpha 6(IV) chain colocalizes with the alpha 5(IV) chain in basement membranes (BMs) of many tissues, but not in glomerular BM. These data exclude the alpha 6(IV) chain as a site for AS mutations. The head-to-head genomic pairing of the alpha 5(IV) and alpha 6 (IV) genes implies coordinate transcription of the two genes. Differential localization of the alpha 5(IV) and alpha 6(IV) chains shows that the two chains are not always coordinately regulated. The alpha 6(IV) chain, together with the alpha 3(IV)-alpha 5(IV) chains, was absent from all renal BMs in eight patients with X-linked AS while the alpha 1(IV) and alpha 2(IV) chains were increased. The data support the existence of two independent collagen networks, one for the alpha 3(IV)-alpha 6(IV) chains and one for the alpha 1(IV) and alpha 2(IV) chains.

我们先前已经表明，α5（IV）和α6（IV）胶原链基因的5'端在Xq22上呈头对头排列，并且在患有Alport综合征（AS）相关弥漫性平滑肌瘤病的患者中缺失。在本研究中，我们制备了兔抗人α6（IV）链抗体，通过分析所有六种IV型链的重组NC1结构域证明了其特异性，并研究了α6（IV）链在涉及AS和弥漫性平滑肌瘤病的成人和胎儿组织中与α1（IV）和α5（IV）链相关的分布情况。α6（IV）链与α5（IV）链在许多组织的基底膜（BMs）中共定位，但在肾小球基底膜中不共定位。这些数据排除了α6（IV）链作为AS突变位点的可能性。α5（IV）和α6（IV）基因的头对头基因组配对意味着这两个基因的协同转录。α5（IV）和α6（IV）链的差异定位表明这两条链并不总是受到协同调节。在八名X连锁AS患者的所有肾基底膜中，α6（IV）链与α3（IV）-α5（IV）链均缺失，而α1（IV）和α2（IV）链增加。这些数据支持存在两个独立的胶原网络，一个由α3（IV）-α6（IV）链组成，另一个由α1（IV）和α2（IV）链组成。