Gene expression analysis of a murine model with pulmonary vascular remodeling compared to end-stage IPAH lungs.
Gene expression analysis of a murine model with pulmonary vascular remodeling compared to end-stage IPAH lungs.
复制标题
与终末期 IPAH 肺相比，肺血管重塑小鼠模型的基因表达分析。
DOI：
10.1186/1465-9921-13-103
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发表时间：
2012-11-17
影响因子：
5.8
通讯作者：
Shibuya K
中科院分区：
文献类型：
--
作者：
Shimodaira K;Okubo Y;Ochiai E;Nakayama H;Katano H;Wakayama M;Shinozaki M;Ishiwatari T;Sasai D;Tochigi N;Nemoto T;Saji T;Kamei K;Shibuya K
特发性肺动脉高压（IPAH）仍然是最严重的难治性疾病之一，可能始于代表患者遗传易感性的几个触发因素的激活。为了阐明IPAH的发病和进展的基本原因，我们研究了在IPAH中起重要作用的因素，通过搜索我们的小鼠模型和先前发表的人IPAH模型之间的差异或有争议的表达模式。我们采用了小鼠模型，通过重复的肺内注射Stachyboasthartarum，一种在我们实验室中普遍存在的非致病性真菌，诱导肺动脉肌化导致高血压。用小鼠肺进行具有本体和途径分析的微阵列测定。比较了我们的模型和IPAH发表的模型之间的生物学途径的表达模式。在我们的模型中，一些途径在IPAH中表现出相同的表达模式，包括骨形态发生蛋白（BMP）信号传导，BMP受体2型、激活素样激酶1型和内皮糖蛋白下调。另一方面，发现Wnt/平面细胞极性（PCP）信号传导及其下游Rho/ROCK信号传导在IPAH中单独被激活，而在我们的模型中没有。Wnt/PCP信号通路的上游位置的激活，在终末期IPAH的肺中单独发现，可能在疾病的发病机制中起重要作用。
Idiopathic pulmonary arterial hypertension (IPAH) continues to be one of the most serious intractable diseases that might start with activation of several triggers representing the genetic susceptibility of a patient. To elucidate what essentially contributes to the onset and progression of IPAH, we investigated factors playing an important role in IPAH by searching discrepant or controversial expression patterns between our murine model and those previously published for human IPAH. We employed the mouse model, which induced muscularization of pulmonary artery leading to hypertension by repeated intratracheal injection of Stachybotrys chartarum, a member of nonpathogenic and ubiquitous fungus in our envelopment. Microarray assays with ontology and pathway analyses were performed with the lungs of mice. A comparison was made of the expression patterns of biological pathways between our model and those published for IPAH. Some pathways in our model showed the same expression patterns in IPAH, which included bone morphogenetic protein (BMP) signaling with down-regulation of BMP receptor type 2, activin-like kinase type 1, and endoglin. On the other hand, both Wnt/planar cell polarity (PCP) signaling and its downstream Rho/ROCK signaling were found alone to be activated in IPAH and not in our model. Activation of Wnt/PCP signaling, in upstream positions of the pathway, found alone in lungs from end stage IPAH may play essential roles in the pathogenesis of the disease.
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影响因子：
4
作者：
Buchsbaum, Rachel J.
通讯作者：
Buchsbaum, Rachel J.
DOI：
10.1152/ajplung.00428.2006
发表时间：
2007-09-01
影响因子：
4.9
作者：
Masri, Fares A.;Xu, Weiling;Erzurum, Serpil C.
通讯作者：
Erzurum, Serpil C.
影响因子：
4.6
作者：
Moreno-Vinasco, Liliana;Gomberg-Maitland, Mardi;Garcia, Joe G. N.
通讯作者：
Garcia, Joe G. N.
影响因子：
5.8
作者：
Kwapiszewska G;Wilhelm J;Wolff S;Laumanns I;Koenig IR;Ziegler A;Seeger W;Bohle RM;Weissmann N;Fink L
通讯作者：
Fink L
影响因子：
5.8
作者：
Maere, S;Heymans, K;Kuiper, M
通讯作者：
Kuiper, M