Overexpression of GDF15 protects kidneys from ischemia reperfusion injury and affects circular RNA expression
Cuilin Zhu1,2, Qing Liu3, Yale Su1,2
1Department of Cardiovascular Surgery, The Second Hospital of Jilin University, Changchun, China.
Background:
Renal failure and dysfunction remain one of the most significant morbidities impacting patient's life. Effective treatments still lack in the context of an increasing number of patients with renal failure. This study aims to investigate the impact of growth differentiation factor 15 (GDF15) in treating renal dysfunction and to explore its therapeutic potential.
Methods:
Renal injury was induced with a murine ischemia reperfusion injury (IRI) model. Mice overexpressing GDF15 (GDF15 transgenic (GDF15TG) mice, GDF15 knock out (GDF15 KO) mice and wild type (WT) mice all underwent IRI to test the effects of GDF15 on renal injury. Renal function and histopathological changes were measured 24 h after reperfusion. Cell apoptosis was detected by TUNEL and tissue inflammation was detected by myeloperoxidase (MPO) activity. qRT-PCR was conducted to determine the expression of genes and circular RNAs.
Results:
Overexpression of GDF15 reduced mortality of mice with lethal renal IRI whereas GDF15 deficiency increased the mortality. GDF15TG mice had better renal function with the lower levels of blood creatinine and blood urea nitrogen (BUN). Over-expression of GDF15 reduced kidney pathological changes, cell apoptosis, neutrophil infiltration and mortality. Over-expression of GDF15 also decreased the expression of apoptotic genes (high mobility group 1, HMGA1 and Bax), inflammatory genes IL-1β, IL-6, tumor necrosis factor (TNF-α), chemokine 1 (CK1), and senescent gene p21 whereas increases Bcl-XL, Importin 11 and CRIM1. IRI upregulated circular RNA Smad3 and reduced circular RNA Hipk3 and circular RNA Crim1, which was offset by GDF15.
Conclusion:
Over-expression of GDF15 protects renal function and prevents renal failure, highlighting its potential in treating renal failure.
Insights
Growth differentiation factor 15 (GDF15) overexpression protects against kidney injury and renal failure in mice. GDF15 deficiency exacerbates kidney damage, indicating its therapeutic potential for renal dysfunction.
Area of Science:
- Nephrology
- Molecular Biology
- Biomedical Research
Background:
- Renal failure and dysfunction are significant morbidities with limited effective treatments.
- The increasing prevalence of renal failure necessitates novel therapeutic strategies.
- Growth differentiation factor 15 (GDF15) is explored for its potential in treating renal dysfunction.
Purpose of the Study:
- To investigate the impact of GDF15 in treating renal dysfunction.
- To explore the therapeutic potential of GDF15 in a murine model of kidney injury.
Main Methods:
- A murine ischemia reperfusion injury (IRI) model was used to induce renal injury.
- GDF15 transgenic (GDF15TG), GDF15 knock out (GDF15 KO), and wild type (WT) mice underwent IRI.
- Renal function, histopathology, apoptosis, inflammation, and gene expression were assessed post-IRI.
Main Results:
- GDF15 overexpression reduced mortality and improved renal function (lower creatinine and BUN) post-IRI.
- GDF15TG mice showed reduced kidney damage, apoptosis, neutrophil infiltration, and mortality.
- GDF15 modulated the expression of key apoptotic, inflammatory, and senescence-related genes and circular RNAs.
Conclusions:
- Overexpression of GDF15 demonstrates a protective effect on renal function.
- GDF15 has the potential to prevent renal failure and warrants further investigation as a therapeutic agent.
