» Articles » PMID: 26004619

Role of GDF15 (growth and Differentiation Factor 15) in Pulmonary Oxygen Toxicity

Overview
Specialty Toxicology
Date 2015 May 26
PMID 26004619
Citations 24
Authors
Affiliations
Soon will be listed here.
Abstract

GDF15 (growth and differentiation factor 15) is a secreted cytokine, a direct target of p53 and plays a role in cell proliferation and apoptosis. It is induced by oxidative stress and has anti-apoptotic effects. The role of GDF15 in hyperoxic lung injury is unknown. We tested the hypothesis that GDF15 will be induced in vitro, in a model of pulmonary oxygen toxicity, and will play a critical role in decreasing cell death and oxidative stress. BEAS-2B (human bronchial epithelial cells) and human pulmonary vascular endothelial cells (HPMEC) were exposed to hyperoxia, and expression of GDF15 and effect of GDF15 disruption on cell viability and oxidative stress was determined. Furthermore, we studied the effect of p53 knockdown on GDF15 expression. In vitro, both BEAS-2B and HPMEC cells showed a significant increase in GDF15 expression upon exposure to hyperoxia. After GDF15 knockdown, there was a significant decrease in cell viability and increase in oxidative stress compared to control cells transfected with siRNA with a scrambled sequence. Knockdown of p53 significantly decreased the induction of GDF15 by hyperoxia. In conclusion, we show that GDF15 has a pro-survival and anti-oxidant role in hyperoxia and that p53 plays a key role in its induction.

Citing Articles

Pretreatment with growth differentiation factor 15 augments cardioprotection by mesenchymal stem cells in myocardial infarction by improving their survival.

Huang X, Liang X, Han Q, Shen Y, Chen J, Li Z Stem Cell Res Ther. 2024; 15(1):412.

PMID: 39523354 PMC: 11550561. DOI: 10.1186/s13287-024-04030-6.


Endothelial to mesenchymal transition in neonatal hyperoxic lung injury: role of sex as a biological variable.

Cantu A, Gutierrez M, Zhang Y, Dong X, Lingappan K Physiol Genomics. 2023; 55(8):345-354.

PMID: 37395632 PMC: 10625841. DOI: 10.1152/physiolgenomics.00037.2023.


Loss of growth differentiation factor 15 exacerbates lung injury in neonatal mice.

Al-Mudares F, Gutierrez M, Cantu A, Jiang W, Wang L, Dong X Am J Physiol Lung Cell Mol Physiol. 2023; 325(3):L314-L326.

PMID: 37368978 PMC: 10625832. DOI: 10.1152/ajplung.00086.2023.


GDF15 as a key disease target and biomarker: linking chronic lung diseases and ageing.

Wan Y, Fu J Mol Cell Biochem. 2023; 479(3):453-466.

PMID: 37093513 PMC: 10123484. DOI: 10.1007/s11010-023-04743-x.


Growth and differentiation factor 15 (GDF15) levels predict adverse respiratory outcomes in premature neonates.

Almudares F, Hagan J, Chen X, Devaraj S, Moorthy B, Lingappan K Pediatr Pulmonol. 2022; 58(1):271-278.

PMID: 36205439 PMC: 9772066. DOI: 10.1002/ppul.26197.


References
1.
Han E, Muller F, Perez V, Qi W, Liang H, Xi L . The in vivo gene expression signature of oxidative stress. Physiol Genomics. 2008; 34(1):112-26. PMC: 2532791. DOI: 10.1152/physiolgenomics.00239.2007. View

2.
Zimmers T, Jin X, Hsiao E, McGrath S, Esquela A, Koniaris L . Growth differentiation factor-15/macrophage inhibitory cytokine-1 induction after kidney and lung injury. Shock. 2005; 23(6):543-8. View

3.
OReilly M, Staversky R, Stripp B, Finkelstein J . Exposure to hyperoxia induces p53 expression in mouse lung epithelium. Am J Respir Cell Mol Biol. 1998; 18(1):43-50. DOI: 10.1165/ajrcmb.18.1.2950m. View

4.
Saugstad O . Bronchopulmonary dysplasia-oxidative stress and antioxidants. Semin Neonatol. 2003; 8(1):39-49. DOI: 10.1016/s1084-2756(02)00194-x. View

5.
Li J, Yang L, Qin W, Zhang G, Yuan J, Wang F . Adaptive induction of growth differentiation factor 15 attenuates endothelial cell apoptosis in response to high glucose stimulus. PLoS One. 2013; 8(6):e65549. PMC: 3683015. DOI: 10.1371/journal.pone.0065549. View