2. Academic Validation
  3. Iron-Quercetin complex enhances mesenchymal stem cell-mediated HGF secretion and c-Met activation to ameliorate acute kidney injury through the prevention of tubular cell apoptosis

Iron-Quercetin complex enhances mesenchymal stem cell-mediated HGF secretion and c-Met activation to ameliorate acute kidney injury through the prevention of tubular cell apoptosis

  • Regen Ther. 2024 Dec 17:28:169-182. doi: 10.1016/j.reth.2024.12.003.
Yuan-Xia Zou 1 2 3,  Jiraporn Kantapan 1,  Hong-Lian Wang 2,  Jian-Chun Li 1 2,  Hong-Wei Su 4,  Jian Dai 2 5,  Nathupakorn Dechsupa 1,  Li Wang 2
Affiliations

Affiliations

  • 1 Molecular Imaging and Therapy Research Unit, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, 50200, Thailand.
  • 2 Research Center for Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, China.
  • 3 Department of Children's Diagnosis and Treatment Center, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, China.
  • 4 Department of Urology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, China.
  • 5 Department of Neurology, The Third People's Hospital, Luzhou, 646000, China.
PMID: 39802634 DOI: 10.1016/j.reth.2024.12.003
Abstract

Background: Acute kidney injury (AKI) is a life-threatening clinical syndrome with no effective treatment currently available. This study aims to investigate whether Iron-Quercetin complex (IronQ) pretreatment can enhance the therapeutic efficacy of Mesenchymal stem cells (MSCs) in AKI and explore the underlying mechanisms.

Methods: A cisplatin-induced AKI model was established in male C57BL/6 mice, followed by the intravenous administration of 1x10ˆ6 MSCs or IronQ-pretreated MSCs (MSCIronQ). Renal function, histology, and tubular cell Apoptosis were analyzed three days post-treatment. In vitro, Apoptosis was induced in mouse tubular epithelial cells (mTECs) using cisplatin, followed by treatment with MSCs or MSCIronQ conditioned medium (CM). Apoptosis was evaluated using TUNEL assay, RT-PCR, and western blotting. Furthermore, RNA Sequencing (RNA-seq) was performed on MSCIronQ to explore the underlying mechanisms.

Results: Compared to MSC-treated AKI mice, those treated with MSCIronQ showed significantly improved renal function and histological outcomes, with reduced tubular cell Apoptosis. A similar effect was observed in cisplatin-treated mTECs exposed to MSCIronQ-CM. Mechanistically, RNA-seq and subsequent validation revealed that IronQ treatment markedly upregulated the expression and secretion of hepatocyte growth factor (HGF) in MSCs. Furthermore, RNA interference or antibody-mediated neutralization of HGF effectively abolished the anti-apoptotic effects of MSCIronQ on mTECs. This mechanistic insight was reinforced by pharmacological inhibition of c-Met, the specific receptor of HGF, in both in vitro and in vivo models.

Conclusions: IronQ pretreatment enhances MSCs efficacy in AKI by promoting HGF expression and secretion, activating the HGF/c-Met pathway to suppress tubular cell Apoptosis. These findings indicate that IronQ improves MSC-based therapies and offers insights into molecular mechanisms, supporting the development of better AKI treatments.

Keywords

Acute kidney injury (AKI); Apoptosis; Hepatocyte growth factor (HGF); Iron-Quercetin complex (IronQ); Mesenchymal stem cells.

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