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Diagnostic Pathology
Published in: Diagnostic Pathology 1/2017

Open Access 01-12-2017 | Research

Implication of overexpression of dishevelled-associated activator of morphogenesis 1 (Daam-1) for the pathogenesis of human Idiopathic Pulmonary Arterial Hypertension (IPAH)

Authors: Shun Yanai, Megumi Wakayama, Haruo Nakayama, Minoru Shinozaki, Hisayuki Tsukuma, Naobumi Tochigi, Tetsuo Nemoto, Tsutomu Saji, Kazutoshi Shibuya

Published in: Diagnostic Pathology | Issue 1/2017

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Abstract

Background

Idiopathic pulmonary arterial hypertension (IPAH) is a rare, fatal disease of unknown pathogenesis. Evidence from our recent study suggests that IPAH pathogenesis is related to upregulation of the Wnt/planar cell polarity (Wnt/PCP) pathway. We used microscopic observation and immunohistochemical techniques to identify expression patterns of cascading proteins—namely Wnt-11, dishevelled-2 (Dvl-2), and dishevelled-associated activator of morphogenesis 1 (Daam-1)—in pulmonary arteries.

Methods

We analyzed sections of formalin-fixed and paraffin-embedded autopsied lung tissues obtained from 9 IPAH cases, 7 associated pulmonary arterial hypertension cases, and 16 age-matched controls without pulmonary arterial abnormalities. Results of microscopic observation were analyzed in relation to the cellular components and size of pulmonary arteries.

Results

Varying rates of positive reactivity to Dvl-2 and Daam-1 were confirmed in all cellular components of pulmonary arteries, namely, endothelial cells, myofibroblasts, and medial smooth muscle cells. In contrast, none of these components was reactive to Wnt-11. No specific expression patterns were observed for endothelial cells or myofibroblasts under any experimental conditions. However, marked expression of Dvl-2 and Daam-1 was confirmed in smooth muscle cells. In addition, Dvl-2 was depleted while Daam-1 expression was elevated in IPAH, in contrast with specimens from associated pulmonary arterial hypertension cases and controls.

Conclusions

High Daam-1 expression may upregulate the Wnt/PCP pathway and cause IPAH.
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Metadata
Title
Implication of overexpression of dishevelled-associated activator of morphogenesis 1 (Daam-1) for the pathogenesis of human Idiopathic Pulmonary Arterial Hypertension (IPAH)
Authors
Shun Yanai
Megumi Wakayama
Haruo Nakayama
Minoru Shinozaki
Hisayuki Tsukuma
Naobumi Tochigi
Tetsuo Nemoto
Tsutomu Saji
Kazutoshi Shibuya
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2017
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/s13000-017-0614-7

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