Shroom expression is attenuated in pulmonary arterial hypertension

¹ Dept of Medicine
² Dept of Pathology, University of Giessen Lung Center, Justus Liebig University Giessen, Giessen, Germany

^* To whom correspondence should be addressed. E-mail: oliver.eickelberg{at}innere.med.uni-giessen.de.

	Abstract

Shroom is a PDZ domain protein involved in the regulation and maintenance of cytoskeletal architecture by binding to actin. Hypertrophy and altered actin organization of pulmonary arterial smooth muscle cells (PASMC) is a hallmark of pulmonary arterial hypertension (PAH). The aim of this study was to localise and characterise Shroom expression in the lung in experimental and idiopathic (I)PAH.

Shroom expression and localization in hypoxia-induced PAH in mice and IPAH in humans in vivo, as well as in primary PASMC in vitro, was assessed by quantitative RT-PCR, immunofluorescence, laser-assisted microdissection, and immunohistochemistry.

Shroom localised exclusively to pulmonary smooth muscle cells (both bronchial and vascular) in mouse and human lungs. In vivo and in primary PASMC in vitro, Shroom exhibited spatially similar expression with -smooth muscle actin (-SMA). Shroom expression was significantly reduced in the mouse model of PAH, in primary murine PASMC exposed to hypoxia, as well as in primary PASMC isolated from patients with IPAH. The ratio between Shroom and SMA RNA expression further confirmed Shroom downregulation in both mouse and human PASMC.

In summary, Shroom localises exclusively to pulmonary smooth muscle cells. Shroom downregulation in PAH suggests a link between Shroom expression and PASMC hypertrophy in PAH.