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GDF-15 in Pulmonary and Critical Care Medicine
- Source :
- American Journal of Respiratory Cell and Molecular Biology, 60(6), 621-628. American Thoracic Society, Am J Respir Cell Mol Biol
- Publication Year :
- 2019
-
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.
- Subjects :
- 0301 basic medicine
Pulmonary and Respiratory Medicine
Senescence
Adult
medicine.medical_specialty
Growth Differentiation Factor 15
Critical Care
Hypertension, Pulmonary
Clinical Biochemistry
Cachexia
Sepsis
03 medical and health sciences
Mice
Pulmonary Disease, Chronic Obstructive
0302 clinical medicine
Neurotrophic factors
medicine
Animals
Humans
Intensive care medicine
Child
Molecular Biology
business.industry
Organ dysfunction
Cell Biology
medicine.disease
Pulmonary hypertension
030104 developmental biology
Translational Review
030228 respiratory system
Heart failure
embryonic structures
GDF15
medicine.symptom
business
Biomarkers
Subjects
Details
- ISSN :
- 10441549
- Database :
- OpenAIRE
- Journal :
- American Journal of Respiratory Cell and Molecular Biology, 60(6), 621-628. American Thoracic Society, Am J Respir Cell Mol Biol
- Accession number :
- edsair.doi.dedup.....270bb2cfb737fa195fe89cfa41fdd0f6