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

Kayoko Shimodaira12, Yoichiro Okubo1, Eri Ochiai34, Haruo Nakayama1, Harutaka Katano5, Megumi Wakayama1*, Minoru Shinozaki1, Takao Ishiwatari1, Daisuke Sasai1, Naobumi Tochigi1, Tetsuo Nemoto1, Tsutomu Saji2, Katsuhiko Kamei3 and Kazutoshi Shibuya16

Author Affiliations

1 Department of Surgical Pathology, Toho University School of Medicine, 6-11-1 Omori-Nishi, Ota-Ku, Tokyo, 143-8541, Japan

2 Department of Pediatrics, Toho University Omori Medical Center, 6-11-1 Omori-Nishi, Ota-Ku, Tokyo, 143-8541, Japan

3 Department of Pathogenic Fungi, Medical Mycology Research Center, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8673, Japan

4 Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY, 40536, USA

5 Department of Pathology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo, 162-8640, Japan

6 Department of Dermatology, Peking University First Hospital, NO.7, Xishiku Street, Xicheng District, Beijing, 100034, China

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Respiratory Research 2012, 13:103  doi:10.1186/1465-9921-13-103

Published: 17 November 2012

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.

Keywords:
Pulmonary Vascular Remodeling; Stachybotrys chartarum; BMP signaling; BMPR2; PCP pathway