Implication of overexpression of dishevelled-associated activator of morphogenesis 1 (Daam-1) for the pathogenesis of human Idiopathic Pulmonary Arterial Hypertension (IPAH).
Diagn Pathol
; 12(1): 25, 2017 Mar 14.
Article
em En
| MEDLINE
| ID: mdl-28288669
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Adaptadoras de Transdução de Sinal
/
Via de Sinalização Wnt
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Hipertensão Pulmonar Primária Familiar
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Adolescent
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Adult
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Female
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Humans
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Infant
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Male
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Middle aged
Idioma:
En
Revista:
Diagn Pathol
Ano de publicação:
2017
Tipo de documento:
Article