ArticleEuropean journal of medical research2023
Hexarelin alleviates apoptosis on ischemic acute kidney injury via MDM2/p53 pathway.
Article in European journal of medical research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 10 citations in OpenAlex.
- Tubule-derived CCN1 drives renal repair via αCell death & disease · 2025Article
- Hesperetin attenuates ischemia/reperfusion-induced acute kidney injury by regulating ferroptosis in mice.Renal failure · 2025Article
- The molecular mechanisms and therapeutic potential of p53 in kidney injury repair: a perspective on the p53alpha/delta133p53alpha signaling axis.Renal failure · 2025Review
- SUMOylation of ZEB1 Modulates PANoptosis in Burn-Induced Early Acute Kidney Injury.Journal of cellular and molecular medicine · 2025Article
- The crosstalk of Wnt/β-catenin signaling and p53 in acute kidney injury and chronic kidney disease.Kidney research and clinical practice · 2024Article
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Authors and funding
15 authors at 3 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
introductionHexarelin exhibits significant protection against organ injury in models of ischemia/reperfusion (I/R)-induced injury (IRI). Nevertheless, the impact of Hexarelin on acute kidney injury (AKI) and its underlying mechanism remains unclear. In this study, we investigated the therapeutic potential of Hexarelin in I/R-induced AKI and elucidated its molecular mechanisms.
methodsWe assessed the protective effects of Hexarelin through both in vivo and in vitro experiments. In the I/R-induced AKI model, rats were pretreated with Hexarelin at 100 μg/kg/d for 7 days before being sacrificed 24 h post-IRI. Subsequently, kidney function, histology, and apoptosis were assessed. In vitro, hypoxia/reoxygenation (H/R)-induced HK-2 cell model was used to investigate the impact of Hexarelin on apoptosis in HK-2 cells. Then, we employed molecular docking using a pharmmapper server and autodock software to identify potential target proteins of Hexarelin.
resultsIn this study, rats subjected to I/R developed severe kidney injury characterized by tubular necrosis, tubular dilatation, increased serum creatinine levels, and cell apoptosis. However, pretreatment with Hexarelin exhibited a protective effect by mitigating post-ischemic kidney pathological changes, improving renal function, and inhibiting apoptosis. This was achieved through the downregulation of conventional apoptosis-related genes, such as Caspase-3, Bax and Bad, and the upregulation of the anti-apoptotic protein Bcl-2. Consistent with the in vivo results, Hexarelin also reduced cell apoptosis in post-H/R HK-2 cells. Furthermore, our analysis using GSEA confirmed the essential role of the apoptosis pathway in I/R-induced AKI. Molecular docking revealed a strong binding affinity between Hexarelin and MDM2, suggesting the potential mechanism of Hexarelin's anti-apoptosis effect at least partially through its interaction with MDM2, a well-known negative regulator of apoptosis-related protein that of p53. To validate these findings, we evaluated the relative expression of MDM2 and p53 in I/R-induced AKI with or without Hexarelin pre-administration and observed a significant suppression of MDM2 and p53 by Hexarelin in both in vivo and in vitro experiments.
conclusionCollectively, Hexarelin was identified as a promising medication in protecting apoptosis against I/R-induced AKI.
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