Tight skin 2 mice exhibit a novel time line of events leading to increased extracellular matrix deposition and dermal fibrosis.
Tight skin 2 mice exhibit a novel time line of events leading to increased extracellular matrix deposition and dermal fibrosis.
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紧致皮肤 2 小鼠表现出新的事件时间线，导致细胞外基质沉积增加和真皮纤维化。
DOI：
10.1016/j.matbio.2014.05.002
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Blankenhorn,ElizabethP
中科院分区：
文献类型：
--
作者：
Long,KristenB;Artlett,CarolM;Blankenhorn,ElizabethP
系统性硬化症（SSc）的紧皮肤2（Tsk 2）小鼠模型具有人类疾病的许多特征，包括紧皮肤、纤维化、细胞外基质异常和报道的抗核抗体（ANA）。在这里，我们报告了Tsk 2/+小鼠随着年龄的增长而发展出过度的真皮纤维化，因为皮肤直到10周才显著纤维化，这是在物理紧皮肤表型发展后整整8周。伴随着两周龄时的紧皮肤表型，Tsk 2/+小鼠表现出总转化生长因子β 1（TGF-β1）水平升高和真皮弹性纤维过度积聚。然而，弹性纤维的增加并不是皮肤紧绷的原因，因为基因工程缺乏皮肤弹性纤维的Tsk 2/+小鼠仍然有皮肤紧绷和纤维化。最后，在第一次可测量的总胶原蛋白增加后约两个月，一部分Tsk 2/+小鼠产生ANA，但与野生型同窝小鼠的水平相似。Tsk 2/+小鼠疾病发展的时间轴显示纤维化是进行性的，弹性纤维改变和TGF-β1过度产生至少发生在纤维化之前两个月，这不依赖于ANA的产生。
The tight skin 2 (Tsk2) mouse model of systemic sclerosis (SSc) has many features of the human disease including tight skin, fibrosis, extracellular matrix abnormalities, and reported antinuclear antibodies (ANA). Here we report that Tsk2/+ mice develop excess dermal fibrosis with age, as skin is not significantly fibrotic until 10 weeks, a full eight weeks after the development of the physical tight skin phenotype. Concomitantly with the tight skin phenotype at two weeks of age, Tsk2/+ mice demonstrate increased levels of total transforming growth factor beta 1 (TGF-β1) and excessive accumulation of dermal elastic fibers. The increase in elastic fibers is not responsible for tight skin, however, because Tsk2/+ mice genetically engineered to lack skin elastic fibers nevertheless have tight skin and fibrosis. Finally, about two months after the first measurable increases of total collagen, a portion of Tsk2/+ mice produce ANAs, but at a similar level to wild-type littermates. The timeline of disease development in the Tsk2/+ mouse shows that fibrosis is progressive, with elastic fiber alterations and TGF-β1 over-production occurring at least two months beforebona fidefibrosis, that is not dependent on ANA production.
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DOI：
--
发表时间：
2015
期刊：
American Review of Respiratory Disease
影响因子：
--
作者：
G. Rossi;G. Hunninghake;J. Gadek;S. Szapiel;O. Kawanami;V. Ferrans;R. Crystal
通讯作者：
R. Crystal
确定系统性硬化症发病机制的策略：转化生长因子 β 是答案吗？
影响因子：
--
作者：
E. Leroy;Edwin A. Smith;M. Kahaleh;M. Trojanowska;R. Silver
通讯作者：
R. Silver
影响因子：
6.9
作者：
Choi, Jiwon;Bergdahl, Andreas;Zheng, Qian;Starcher, Barry;Yanagisawa, Hiromi;Davis, Elaine C.
通讯作者：
Davis, Elaine C.
影响因子：
7
作者：
Siracusa, LD;McGrath, R;Jimenez, SA
通讯作者：
Jimenez, SA
硬皮病的抗纤维化治疗：细胞外或细胞内靶向活化的成纤维细胞？
影响因子：
5
作者：
J. Varga
通讯作者：
J. Varga