title: 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.
authors.affiliation: Department of Surgical Pathology, Toho University School of Medicine, 6-11-1 Omori-Nishi, Ota-Ku, Tokyo 143-8541, Japan.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Shimodaira
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Okubo
authors.forename: Eri
authors.initials: E
authors.lastname: Ochiai
authors.forename: Haruo
authors.initials: H
authors.lastname: Nakayama
authors.forename: Harutaka
authors.initials: H
authors.lastname: Katano
authors.forename: Megumi
authors.initials: M
authors.lastname: Wakayama
authors.forename: Minoru
authors.initials: M
authors.lastname: Shinozaki
authors.forename: Takao
authors.initials: T
authors.lastname: Ishiwatari
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sasai
authors.forename: Naobumi
authors.initials: N
authors.lastname: Tochigi
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nemoto
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Saji
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Kamei
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Shibuya
mesh_terms: D000818:Animals; D016764:Cell Polarity; D002648:Child; D002675:Child, Preschool; D065627:Familial Primary Pulmonary Hypertension; D005786:Gene Expression Regulation; D006801:Humans; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D008168:Lung / Q000503:physiopathology*; D008297:Male; D051379:Mice; D020543:Proteome / Q000378:metabolism*; D011651:Pulmonary Artery / Q000503:physiopathology*; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D020543:Proteome; D051153:Wnt Proteins