Down-regulation of the inhibitor of growth family member 4 (ING4) in different forms of pulmonary fibrosis

doi:10.1186/1465-9921-10-14

Respiratory Research

Volume 10

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Tzouvelekis A
Aidinis V
Harokopos V
Karameris A
Zacharis G
Mikroulis D
Konstantinou F
Steiropoulos P
Sotiriou I
Froudarakis M
Pneumatikos I
Tringidou R
Bouros D

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Tzouvelekis A
Aidinis V
Harokopos V
Karameris A
Zacharis G
Mikroulis D
Konstantinou F
Steiropoulos P
Sotiriou I
Froudarakis M
Pneumatikos I
Tringidou R
Bouros D
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Research

Down-regulation of the inhibitor of growth family member 4 (ING4) in different forms of pulmonary fibrosis

Argyris Tzouvelekis¹ , Vassilis Aidinis² , Vagelis Harokopos² , Andreas Karameris³ , George Zacharis¹ , Dimitrios Mikroulis⁴ , Fotios Konstantinou⁴ , Paschalis Steiropoulos¹ , Ioannis Sotiriou¹ , Marios Froudarakis¹ , Ioannis Pneumatikos⁵ , Rodoula Tringidou⁶ and Demosthenes Bouros¹

¹Department of Pneumonology, University Hospital of Alexandroupolis, Medical school, Democritus University of Thrace, Greece

²Institute of Immunology, Biomedical Sciences Research Center "Alexander Fleming", Athens, Greece

³Department of Pathology, VA Hospital (NIMTS), Athens, Greece

⁴Department of Cardiothoracic Surgery, University Hospital of Alexandroupolis, Medical school, Democritus University of Thrace, Greece

⁵Department of Intensive Care Medicine, University Hospital of Alexandroupolis, Medical school, Democritus University of Thrace, Greece

⁶Department of Pathology, General Hospital Sotiria, Athens, Greece

author email corresponding author email

Respiratory Research 2009, 10:14doi:10.1186/1465-9921-10-14


Published:	27 February 2009

Abstract

Background

Recent evidence has underscored the role of hypoxia and angiogenesis in the pathogenesis of idiopathic fibrotic lung disease. Inhibitor of growth family member 4 (ING4) has recently attracted much attention as a tumor suppressor gene, due to its ability to inhibit cancer cell proliferation, migration and angiogenesis. The aim of our study was to investigate the role of ING4 in the pathogenesis of pulmonary fibrosis both in the bleomycin (BLM)-model and in two different types of human pulmonary fibrosis, including idiopathic pulmonary fibrosis (IPF) and cryptogenic organizing pneumonia (COP).

Methods

Experimental model of pulmonary fibrosis was induced by a single tail vein injection of bleomycin in 6- to 8-wk-old C57BL/6mice. Tissue microarrays coupled with qRT-PCR and immunohistochemistry were applied in whole lung samples and paraffin-embedded tissue sections of 30 patients with IPF, 20 with COP and 20 control subjects.

Results

A gradual decline of ING4 expression in both mRNA and protein levels was reported in the BLM-model. ING4 was also found down-regulated in IPF patients compared to COP and control subjects. Immunolocalization analyses revealed increased expression in areas of normal epithelium and in alveolar epithelium surrounding Masson bodies, in COP lung, whereas showed no expression within areas of active fibrosis within IPF and COP lung. In addition, ING4 expression levels were negatively correlated with pulmonary function parameters in IPF patients.

Conclusion

Our data suggest a potential role for ING4 in lung fibrogenesis. ING4 down-regulation may facilitate aberrant vascular remodelling and fibroblast proliferation and migration leading to progressive disease.