Regulation of collagen type IV genes is organ-specific: evidence from a canine model of Alport syndrome.
Regulation of collagen type IV genes is organ-specific: evidence from a canine model of Alport syndrome.
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IV 型胶原蛋白基因的调节具有器官特异性：来自阿尔波特综合征犬模型的证据。
DOI：
10.1111/j.1523-1755.2005.00668.x
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Thorner,PaulS
中科院分区：
文献类型：
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作者：
Zheng,Keqin;Perry,Julie;Harvey,ScottJ;Sado,Yoshikazu;Ninomiya,Yoshifumi;Jefferson,Barbara;Jacobs,Robert;Hudson,BillyG;Thorner,PaulS
IV型胶原蛋白基因的调节是器官特异性的：来自阿尔波特综合征犬模型的证据。尽管在蛋白水平上对IV型胶原的认识有所进展，但对其6条α链的表达知之甚少。x连锁Alport综合征提供了一个系统来研究胶原IV型基因在蛋白质合成紊乱的情况下的表达。α5链的突变导致肾脏α3/α4/α5和α1/α2/α5/α6网络的丢失，并伴有肾脏疾病的进展。方法采用犬Alport综合征模型，测定11 ~ 7个半月大鼠6条IV型胶原链的表达。我们确定了肾脏中信息水平随时间变化的程度，以及肾小球的临床和病理变化以及原发性突变之间存在的相关性。后者通过检查睾丸来评估，睾丸通常含有相同的胶原蛋白IV型网络，但未受疾病影响。结果α1 ~ α6 mrna在正常犬肾组织各时间点均有表达。与正常相比，Alport狗肾脏中α1、α2 mRNA在2月龄时上调，α3、α4 mRNA在2月龄时下调，α5 mRNA在任何时候几乎检测不到。在睾丸中，除α5链外，所有mrna在正常犬和患犬中表达水平相当，α5链在患犬中不表达。结论IV型胶原蛋白的正常表达受各器官和各细胞链特异性调控机制的影响。犬Alport综合征的表达改变不是突变的直接结果，因为这些变化不是发生在所有器官中，也不是从出生起就存在。相反，IV型胶原的表达受疾病的影响，α3和α4链的下调与蛋白尿的发生有时间关系，α1和α2链的上调与肾小球硬化有关。α3和α4链的失调是这种Alport模型所特有的，表明这两条链的表达下调与病理联系的机制尚未确定。
Regulation of collagen type IV genes is organ-specific: Evidence from a canine model of Alport syndrome.BackgroundDespite advances in knowledge about collagen type IV at the protein level, little is known about expression of its six α chains. X-linked Alport syndrome provides a system to study collagen type IV gene expression within a setting of disturbed protein synthesis. Mutations in the α5 chain result in loss of the α3/α4/α5 and α1/α2/α5/α6 networks from the kidney, with progressive renal disease.MethodsWe used a canine model of Alport syndrome to measure expression of the six type IV collagen chains from 11 days to 71/2 months of age. We determined to what extent message levels in kidney change over time, and what correlation exists with clinical and pathologic changes in glomeruli, and the primary mutation. The latter was evaluated by examining testis, an organ normally containing the same collagen type IV networks but uninvolved by disease.ResultsThe α1 to α6 mRNAs were expressed at all time points in normal canine kidney. By comparison to normal, in Alport dog kidney, the α1 and α2 mRNAs were up-regulated after 2 months of age, α3 and α4 mRNAs were down-regulated by 2 months of age, and the α5 mRNA was almost undetectable at any time. In testis, all mRNAs were expressed at comparable levels in normal and affected dogs other than the α5 chain, which was not expressed in affected testis.ConclusionNormal expression of collagen type IV is under control mechanisms specific to each organ and to individual chains. The altered expression in canine Alport syndrome is not the direct result of the mutation, since these changes do not occur in all organs nor are they present from birth. Instead, collagen type IV expression is influenced by disease, with down-regulation of α3 and α4 chains temporally related to the onset of proteinuria, and up-regulation of α1 and α2 chains to glomerulosclerosis. This dysregulation of the α3 and α4 chains is unique to this Alport model, and suggests an unidentified mechanism linking pathology with down-regulation of expression of these two chains.
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影响因子：
19.6
作者：
GUO, CY;VANDAMME, B;MARYNEN, P
通讯作者：
MARYNEN, P
DOI：
10.1073/pnas.91.24.11679
发表时间：
1994-11-22
影响因子：
11.1
作者：
SUGIMOTO, M;OOHASHI, T;NINOMIYA, Y
通讯作者：
NINOMIYA, Y
影响因子：
4.8
作者：
Sampson, NS;Ryan, ST;Gotwals, P
通讯作者：
Gotwals, P
影响因子：
1
作者：
G. Lees;Helman Rg;C. Kashtan;A. Michael;L. Homco;N. Millichamp;Camacho Zt;J. Templeton;Y. Ninomiya;Y. Sado;I. Naito;Youngki Kim
通讯作者：
G. Lees;Helman Rg;C. Kashtan;A. Michael;L. Homco;N. Millichamp;Camacho Zt;J. Templeton;Y. Ninomiya;Y. Sado;I. Naito;Youngki Kim
Kenji Saito、Ichiro Naito、Tsugio Seki、Toshitaka Oohashi、Eiki Kimura、Ryusuke Momota、Yumiko Kishiro、Yoshikazu Sado、Hidekatsu Yoshioka 和 Yoshifumi Ninomiya：“小鼠 α5(IV) 和 α6(IV) 胶原蛋白基因在上皮基底细胞中的差异表达
DOI：
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