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Gremlin localization and expression levels partially differentiate idiopathic interstitial pneumonia severity and subtype.
J Pathol. 2008 Mar; 214(4):456-63.JP

Abstract

Idiopathic pulmonary fibrosis (IPF) (histopathology of usual interstitial pneumonia, UIP) and non-specific interstitial pneumonia (NSIP) are diseases characterized by loss of normal lung architecture and function. The differential diagnosis between IPF/UIP and NSIP may be difficult. The levels of bone morphogenetic protein (BMP)-4 antagonist gremlin are up-regulated in IPF/UIP. The present study was performed to clarify whether the localization or the mRNA expression of gremlin or BMP-4 could be used in the differential diagnosis or assessment of severity of IPF/UIP and NSIP. Gremlin and BMP-4 immunoreactivities were quantitated from 24 UIP and 12 NSIP lung specimens. Quantitative real-time polymerase chain reaction analyses were performed to compare gremlin and BMP-4 expression between UIP (n = 8) and NSIP (n = 5) biopsies. Immunohistochemical positivity and mRNA levels were correlated to lung function parameters. In IPF/UIP biopsies, gremlin was detected mainly in the thickened lung parenchyma, whereas in NSIP it was observed in the alveolar epithelium. BMP-4-positive (BMP-4+) cells were detected solely in the alveolar wall. The percentage of gremlin-positive area was higher in IPF/UIP (5.1 +/- 0.6) than in NSIP (1.8 +/- 0.7) (n = 36, p < 0.0001). Gremlin mRNA levels were higher in advanced UIP (p = 0.008) and NSIP (p = 0.007) biopsies than in the normal control lung. A negative correlation was found between the specific diffusion capacity corrected for alveolar volume (DLCO/VA) and gremlin mRNA levels (r = - 0.69, p = 0.007). The highest numbers of BMP-4+ cells were found in NSIP biopsies. BMP-4 mRNA levels correlated positively with forced vital capacity (r = 0.801, p < 0.0001) and diffusion capacity. Parenchymal gremlin immunoreactivity is thus suggestive of a UIP-type interstitial pneumonia. Gremlin expression levels correlating negatively and BMP-4 levels positively with disease severity support recent observations of a fibroprotective role for the BMPs.

Authors+Show Affiliations

Department of Medicine and Division of Pulmonary Medicine, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. marjukka.myllarniemi@helsinki.fiNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Evaluation Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18072275

Citation

Myllärniemi, M, et al. "Gremlin Localization and Expression Levels Partially Differentiate Idiopathic Interstitial Pneumonia Severity and Subtype." The Journal of Pathology, vol. 214, no. 4, 2008, pp. 456-63.
Myllärniemi M, Vuorinen K, Pulkkinen V, et al. Gremlin localization and expression levels partially differentiate idiopathic interstitial pneumonia severity and subtype. J Pathol. 2008;214(4):456-63.
Myllärniemi, M., Vuorinen, K., Pulkkinen, V., Kankaanranta, H., Aine, T., Salmenkivi, K., Keski-Oja, J., Koli, K., & Kinnula, V. (2008). Gremlin localization and expression levels partially differentiate idiopathic interstitial pneumonia severity and subtype. The Journal of Pathology, 214(4), 456-63.
Myllärniemi M, et al. Gremlin Localization and Expression Levels Partially Differentiate Idiopathic Interstitial Pneumonia Severity and Subtype. J Pathol. 2008;214(4):456-63. PubMed PMID: 18072275.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gremlin localization and expression levels partially differentiate idiopathic interstitial pneumonia severity and subtype. AU - Myllärniemi,M, AU - Vuorinen,K, AU - Pulkkinen,V, AU - Kankaanranta,H, AU - Aine,T, AU - Salmenkivi,K, AU - Keski-Oja,J, AU - Koli,K, AU - Kinnula,Vl, PY - 2007/12/12/pubmed PY - 2008/4/24/medline PY - 2007/12/12/entrez SP - 456 EP - 63 JF - The Journal of pathology JO - J. Pathol. VL - 214 IS - 4 N2 - Idiopathic pulmonary fibrosis (IPF) (histopathology of usual interstitial pneumonia, UIP) and non-specific interstitial pneumonia (NSIP) are diseases characterized by loss of normal lung architecture and function. The differential diagnosis between IPF/UIP and NSIP may be difficult. The levels of bone morphogenetic protein (BMP)-4 antagonist gremlin are up-regulated in IPF/UIP. The present study was performed to clarify whether the localization or the mRNA expression of gremlin or BMP-4 could be used in the differential diagnosis or assessment of severity of IPF/UIP and NSIP. Gremlin and BMP-4 immunoreactivities were quantitated from 24 UIP and 12 NSIP lung specimens. Quantitative real-time polymerase chain reaction analyses were performed to compare gremlin and BMP-4 expression between UIP (n = 8) and NSIP (n = 5) biopsies. Immunohistochemical positivity and mRNA levels were correlated to lung function parameters. In IPF/UIP biopsies, gremlin was detected mainly in the thickened lung parenchyma, whereas in NSIP it was observed in the alveolar epithelium. BMP-4-positive (BMP-4+) cells were detected solely in the alveolar wall. The percentage of gremlin-positive area was higher in IPF/UIP (5.1 +/- 0.6) than in NSIP (1.8 +/- 0.7) (n = 36, p < 0.0001). Gremlin mRNA levels were higher in advanced UIP (p = 0.008) and NSIP (p = 0.007) biopsies than in the normal control lung. A negative correlation was found between the specific diffusion capacity corrected for alveolar volume (DLCO/VA) and gremlin mRNA levels (r = - 0.69, p = 0.007). The highest numbers of BMP-4+ cells were found in NSIP biopsies. BMP-4 mRNA levels correlated positively with forced vital capacity (r = 0.801, p < 0.0001) and diffusion capacity. Parenchymal gremlin immunoreactivity is thus suggestive of a UIP-type interstitial pneumonia. Gremlin expression levels correlating negatively and BMP-4 levels positively with disease severity support recent observations of a fibroprotective role for the BMPs. SN - 0022-3417 UR - https://www.unboundmedicine.com/medline/citation/18072275/Gremlin_localization_and_expression_levels_partially_differentiate_idiopathic_interstitial_pneumonia_severity_and_subtype_ L2 - https://doi.org/10.1002/path.2300 DB - PRIME DP - Unbound Medicine ER -