Gremlin localization and expression levels partially differentiate idiopathic interstitial pneumonia severity and
M Myllärniemi1, K Vuorinen, V Pulkkinen
1Department of Medicine and Division of Pulmonary Medicine, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. marjukka.myllarniemi@helsinki.fi
The Journal of Pathology
|December 12, 2007
Summary
Parenchymal gremlin is a potential biomarker for differentiating idiopathic pulmonary fibrosis (IPF) from non-specific interstitial pneumonia (NSIP). Gremlin and BMP-4 levels correlate with disease severity, aiding in diagnosis and assessment.
Area of Science:
- Pulmonary Medicine
- Pathology
- Molecular Biology
Background:
- Idiopathic pulmonary fibrosis (IPF) and non-specific interstitial pneumonia (NSIP) are lung diseases causing architectural and functional loss.
- Differentiating between IPF/UIP and NSIP can be challenging.
- Gremlin, a bone morphogenetic protein (BMP)-4 antagonist, is upregulated in IPF/UIP.
Purpose of the Study:
- To investigate if gremlin and BMP-4 localization or mRNA expression can aid in differential diagnosis and severity assessment of IPF/UIP and NSIP.
- To correlate gremlin and BMP-4 expression with lung function parameters.
Main Methods:
- Quantification of gremlin and BMP-4 immunoreactivity in 24 UIP and 12 NSIP lung specimens.
- Quantitative real-time PCR for gremlin and BMP-4 mRNA expression in UIP (n=8) and NSIP (n=5) biopsies.
- Correlation analysis of protein and mRNA levels with lung function parameters.
Main Results:
- Gremlin was mainly detected in thickened lung parenchyma in IPF/UIP and alveolar epithelium in NSIP.
- Gremlin-positive area was significantly higher in IPF/UIP than NSIP (p < 0.0001).
- Gremlin mRNA levels were elevated in advanced UIP and NSIP compared to controls.
- BMP-4 positive cells were found in the alveolar wall, with higher numbers in NSIP.
- Gremlin mRNA levels negatively correlated with diffusion capacity (DLCO/VA) (r = -0.69, p = 0.007).
- BMP-4 mRNA levels positively correlated with forced vital capacity (r = 0.801, p < 0.0001) and diffusion capacity.
Conclusions:
- Parenchymal gremlin immunoreactivity suggests a UIP-type interstitial pneumonia.
- Gremlin and BMP-4 expression levels correlate with disease severity, supporting a fibroprotective role for BMPs.
- Gremlin and BMP-4 may serve as diagnostic and prognostic markers in interstitial lung diseases.
