Abstract: FR-PO0295
MET Receptor and Its Endogenous Ligand Hepatocyte Growth Factor (HGF) Are Differently Regulated in Acute and Subchronic Rat Models of Diabetes
Session Information
- Diabetic Kidney Disease: Basic and Translational Science Advances - 1
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 701 Diabetic Kidney Disease: Basic
Authors
- Hadova, Katarina, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University Bratislava, Bratislava, Slovakia
- Mesarosova, Lucia, Department of (Neuro) Pathology, Amsterdam Neuroscience, Amsterdam UMC location University of Amsterdam, Amsterdam, Netherlands
- Cinakova, Aneta, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University Bratislava, Bratislava, Slovakia
- Kralova, Eva, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University Bratislava, Bratislava, Slovakia
- Krenek, Peter, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University Bratislava, Bratislava, Slovakia
- Klimas, Jan, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University Bratislava, Bratislava, Slovakia
Background
The MET receptor plays an essential role in normal kidney development, injury repair, and regeneration. It is activated by high glucose levels independently of its endogenous ligand, HGF, in human tubule epithelial cells (HK-2), which may be significant in diabetic nephropathy. This study aimed to investigate the MET receptor in the kidneys of rats affected by diabetes mellitus (DM).
Methods
DM was induced in Wistar rats by an intraperitoneal (i.p.) streptozotocin injection. Controls were injected with vehicle i.p. Rats with blood glucose ≥ 12 mmol/L, measured after 3 days, were considered diabetic. The diabetic rats remained untreated for either 10 days or 6 weeks to investigate the effects of acute and subchronic DM conditions. To confirm kidney damage, histological sections from the subchronic model were stained with PAS and Picro-Mallory-Trichrome and in both models, KIM1 mRNA expression was measured by RT-qPCR. MET and its downstream molecules were assessed by Western blotting. Plasma HGF was determined by ELISA.
Results
Histology revealed increased glomerulosclerosis and numerous fibrotic lesions in diabetic kidneys. Urine creatinine and microalbumin levels were elevated. KIM1 expression was increased in both models. Importantly, we found substantially increased phosphorylation of the MET receptor in the kidneys of rats with subchronic DM (57%; P<0.05); however, MET protein was downregulated (-36%; P<0.05). In acute DM, there was no significant change in the renal MET protein levels. Interestingly, in the subchronic model, the downstream molecule AKT, but not ERK1/2, had enhanced phosphorylation (105%; P<0.05). Moreover, protein expression of HGF was increased in the subchronic model (29%; P<0.05) but remained unchanged in the acute model and we even observed downregulation of Hgf gene (-53%; P<0.05). Plasma HGF levels did not change in either model.
Conclusion
Our study found increased activation of the MET receptor in kidneys affected by DM. Hyperglycemia, as well as upregulated HGF, may contribute to this effect. The expression of MET and HGF is altered as the disease progresses. Increased activation of HGF/MET pathway may serve as compensatory mechanism against kidney damage due to DM. Funding: Project was supported by grant APVV-23-0502 and VEGA 1/0707/25.
Funding
- Government Support – Non-U.S.