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Published on: November 10, 2021
Apelin protects against acute renal injury by inhibiting TGF-β1
Hong Chen1, Danyang Wan2, Lin Wang2
1Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, China, 430030; Centre for Biomedicine Research, Wuhan Institute of Biotechnology, Wuhan, China, 430074.
Abstract:
Renal ischemia/reperfusion (I/R) injury is the most common cause of acute kidney injury, having a high rate of mortality and no effective therapy currently available. Apelin-13, a bioactive peptide, has been shown to inhibit the early lesions of diabetic nephropathy in several mouse models by us and others. To test whether apelin-13 protects against renal I/R induced injury, male rats were exposed to renal I/R injury with or without apelin-13 treatment for 3 days. Apelin-13 treatment markedly reduced the injury-induced tubular lesions, renal cell apoptosis, and normalized the injury induced renal dysfunction. Apelin-13 treatment inhibited the injury-induced elevation of inflammatory factors and Tgf-β1, as well as apoptosis. Apelin-13 treatment also inhibited the injury-induced elevation of histone methylation and Kmt2d, a histone methyltransferase of H3K4me2, following renal I/R injury. Furthermore, in cultured renal mesangial and tubular cells, apelin-13 suppressed the injury-induced elevation of Tgf-β1, apoptosis, H3K4me2 and Kmt2d under the in vitro hypoxia/reperfusion (H/R) conditions. Consistently, over-expression of apelin significantly inhibited H/R-induced elevation of TGF-β1, apoptosis, H3K4me2 and Kmt2d. The present study therefore suggests apelin-13 may be a therapeutic candidate for treating acute kidney injury.
Insights
Apelin-13 peptide effectively protects against acute kidney injury caused by renal ischemia/reperfusion (I/R). This treatment reduces kidney damage, inflammation, and cell death, suggesting its therapeutic potential.
Area of Science:
- Nephrology
- Molecular Biology
- Cell Biology
Background:
- Renal ischemia/reperfusion (I/R) injury is a primary cause of acute kidney injury (AKI) with high mortality.
- Current therapies for AKI lack effectiveness.
- Apelin-13, a bioactive peptide, has demonstrated protective effects in diabetic nephropathy models.
Purpose of the Study:
- To investigate the protective effects of apelin-13 against renal I/R injury in a rat model.
- To explore the molecular mechanisms underlying apelin-13's renoprotective actions.
Main Methods:
- Male rats were subjected to renal I/R injury with or without apelin-13 treatment.
- In vitro studies utilized cultured renal mesangial and tubular cells exposed to hypoxia/reperfusion (H/R).
- Assessed tubular lesions, apoptosis, renal dysfunction, inflammatory factors, TGF-β1, histone methylation (H3K4me2), and Kmt2d expression.
Main Results:
- Apelin-13 treatment significantly reduced tubular lesions, renal cell apoptosis, and normalized renal dysfunction post-I/R.
- Apelin-13 inhibited the elevation of inflammatory factors, TGF-β1, and apoptosis induced by I/R.
- Apelin-13 suppressed I/R-induced increases in histone methylation (H3K4me2) and Kmt2d in vivo and in vitro.
Conclusions:
- Apelin-13 demonstrates significant renoprotective effects against I/R injury by mitigating inflammation and apoptosis.
- The mechanism involves the inhibition of TGF-β1 and aberrant histone methylation.
- Apelin-13 presents a promising therapeutic candidate for acute kidney injury.
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