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GDF-15 in Pulmonary and Critical Care Medicine.

Authors
  • Verhamme, Fien M1
  • Freeman, Christine M2, 3, 4
  • Brusselle, Guy G1, 5, 6
  • Bracke, Ken R1
  • Curtis, Jeffrey L2, 3, 4
  • 1 1 Department of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium. , (Belgium)
  • 2 2 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, and.
  • 3 3 Graduate Program in Immunology, University of Michigan Medical School, Ann Arbor, Michigan.
  • 4 4 VA Ann Arbor Healthcare System, Ann Arbor, Michigan; and.
  • 5 5 Department of Epidemiology and.
  • 6 6 Department of Respiratory Medicine, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands. , (Netherlands)
Type
Published Article
Journal
American Journal of Respiratory Cell and Molecular Biology
Publisher
American Thoracic Society
Publication Date
Jun 01, 2019
Volume
60
Issue
6
Pages
621–628
Identifiers
DOI: 10.1165/rcmb.2018-0379TR
PMID: 30633545
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

GDF-15 (growth differentiation factor 15) acts both as a stress-induced cytokine with diverse actions at different body sites and as a cell-autonomous regulator linked to cellular senescence and apoptosis. For multiple reasons, this divergent transforming growth factor-β molecular superfamily member should be better known to pulmonary researchers and clinicians. In ambulatory individuals, GDF-15 concentrations in peripheral blood are an established predictive biomarker of all-cause mortality and of adverse cardiovascular events. Concentrations upon admission of critically ill patients (without or with sepsis) correlate with organ dysfunction and independently predict short- and long-term mortality risk. GDF-15 is a major downstream mediator of p53 activation, but it can also be induced independently of p53, notably by nonsteroidal antiinflammatory agents. GDF-15 blood concentrations are markedly elevated in adults and children with pulmonary hypertension. Concentrations are also increased in chronic obstructive pulmonary disease, in which they contribute to mucus hypersecretion, airway epithelial cell senescence, and impaired antiviral defenses, which together with murine data support a role for GDF-15 in chronic obstructive pulmonary disease pathogenesis and progression. This review summarizes biological and clinical data on GDF-15 relevant to pulmonary and critical care medicine. We highlight the recent discovery of a central nervous system receptor for GDF-15, GFRAL (glial cell line-derived neurotrophic factor family receptor-α-like), an important advance with potential for novel treatments for obesity and cachexia. We also describe limitations and controversies in the existing literature, and we delineate research questions that must be addressed to determine whether GDF-15 can be therapeutically manipulated in other clinical settings.

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