Abstract: SA-PO0934
Protective Role of miR-125b Inhibition in Metabolic Kidney Failure
Session Information
- Pathology: Updates and Insights
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pathology and Lab Medicine
- 1800 Pathology and Lab Medicine
Authors
- Hueso, Miguel, Hospital Universitari de Bellvitge Servei de Nefrologia, L'Hospitalet de Llobregat, Catalunya/Barcelona, Spain
- Mallén Bareas, Adrián, Institut d'Investigacio Biomedica de Bellvitge, L'Hospitalet de Llobregat, Catalunya/Barcelona, Spain
- Bertolino, Elena, Institut d'Investigacio Biomedica de Bellvitge, L'Hospitalet de Llobregat, Catalunya/Barcelona, Spain
- Torras, Joan, Hospital Universitari de Bellvitge Servei de Nefrologia, L'Hospitalet de Llobregat, Catalunya/Barcelona, Spain
- Suñé-Pou, Marc, Universitat de Barcelona, Barcelona, Catalunya/Barcelona, Spain
- Ara, Jordi, Hospital Universitari Germans Trias i Pujol, Badalona, Catalunya/Barcelona, Spain
- Bover, Jordi, Hospital Universitari Germans Trias i Pujol, Badalona, Catalunya/Barcelona, Spain
Background
miR-125b accelerates atherosclerosis in ApoE-/-mice, and blocking it with a specific antagomiR can reverse this effect. However, the systemic administration of nucleic acids may induce off-target effects due to nonspecific immune system stimulation, causing kidney damage.
This study aimed to evaluate the impact of miR-125b administration on kidney function in the ApoE-/- model.
Methods
We included 48 ApoE-/- mice aged 8 w, fed a high-cholesterol diet for 14 w. From week 10 of the diet, mice received subcutaneous administration for 4 w of: i) PBS (control); ii) antagomiR with a scrambled sequence (SC); iii) miR-125b; iv) specific antagomiR; v) Cy5-labeled antagomiR (12 mice per group, 6 males (M) and 6 females (F)). We evaluated weight, blood pressure, kidney function (creatinine, creatinine clearance, proteinuria), and metabolic profile. Samples were collected for histological analysis.
Results
miR-125b impaired kidney function, while the antagomiR was protective in males [Cr = 2.58±2.27 mg/dL in PBS, 3.05±2.18 in SC, 4.56±1.98 in miR-125b vs. 1.90±1.78 in antagomiR, p=0.02].
Sex differences were observed: males had a higher body weight (22.6±1.9 g in F vs. 29.4±1.1 g in M, p<0.01), exhibited higher proteinuria (177±98 mg in F vs. 1236±674 in M, p<0.01), and lower creatinine clearance. miR-125b had a deleterious effect on kidney function, whereas the antagomiR showed a protective effect in M (PBS: ClCr = 0.028±0.024 mL/min in F vs. 0.008±0.08 in M; miR-125b: 0.010±0.006 in F vs. 0.003±0.005 in M; antagomiR: 0.015±0.008 in F vs. 0.028±0.025 in M; p=0.011). Tubular creatinine secretion was reduced in the miR-125b-treated group. Additionally, the Cy5-labeled antagomiR indicated a preference for miR-125b localization in the proximal tubule. Females showed higher LDL-cholesterol levels [21.8±9.4 mmol/L in F vs. 13.6±8.1 in M; p=0.002], and miR-125b did not influence these levels. Renal histological analysis is currently ongoing.
Conclusion
In this metabolic disease model, males exhibited more severe kidney dysfunction and higher proteinuria levels. miR-125b had a deleterious effect on kidney function, while the antagomiR had a protective effect, with the response influenced by sex.
It is hypothesized that miR-125b reduces creatinine secretion, while blocking it increases creatinine clearance in males without altering proteinuria levels
Funding
- Government Support – Non-U.S.