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Gene expression analysis of a murine model with pulmonary vascular remodeling compared to end-stage IPAH lungs.

Abstract：

BACKGROUND: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. METHODS: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. RESULTS: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. CONCLUSIONS: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.

journal_name

Respir Res

journal_title

Respiratory research

authors

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

doi

10.1186/1465-9921-13-103

subject

Has Abstract

pub_date

2012-11-17 00:00:00

pages

103

eissn

1465-9921

issn

1465-993X

pii

1465-9921-13-103

journal_volume

13

pub_type

杂志文章

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