Abstract: TH-PO0395
miR-125b Inhibition Uncouples Inflammation from Blood Pressure: A Sex-Specific Mechanism of Glomerular Injury
Session Information
- Glomerular Diseases: Genetics to Therapeutics
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Women's Health and Kidney Diseases
- 2100 Women's Health and Kidney Diseases
Authors
- Hueso, Miguel, Hospital Universitari de Bellvitge Servei de Nefrologia, L'Hospitalet de Llobregat, CT, Spain
- Mallén Bareas, Adrián, Fundacio Institut d'Investigacio en Ciencies de la Salut Germans Trias i Pujol, Badalona, CT, Spain
- Rotllan, Noemi, Institut Recerca Sant Pau, Barcelona, CT, Spain
- Griñan Gonzalez, Raquel, Institut Recerca Sant Pau, Barcelona, CT, Spain
- Escola-Gil, Joan Carles, Institut Recerca Sant Pau, Barcelona, CT, Spain
- Torras, Joan, Hospital Universitari de Bellvitge Servei de Nefrologia, L'Hospitalet de Llobregat, CT, Spain
- Suñé-Pou, Marc, Barcelona University, Barcelona, CT, Spain
- Navarro, Estanis, Fundacio Institut d'Investigacio en Ciencies de la Salut Germans Trias i Pujol, Badalona, CT, Spain
- Ara, Jordi, Hospital Universitari Germans Trias i Pujol, Badalona, CT, Spain
- Bover, Jordi, Hospital Universitari Germans Trias i Pujol, Badalona, CT, Spain
Background
Sex differences critically influence hypertension and chronic kidney disease, yet underlying molecular mechanisms remain unclear. MicroRNA-125b (miR-125b) regulates vascular inflammation and targets endothelin-1 (ET-1), a key mediator of vasoconstriction. We hypothesized that miR-125b inhibition exerts sex-specific effects on glomerular injury through differential inflammatory and hemodynamic responses.
Methods
Thirty-six 18-week-old ApoE kockout mice (18 males and 18 females) were treated for 4w with miR-125b (15 mg/kg), antagomiR-125b, or scrambled (SC) control. Glomerular injury was quantified by digital morphometry as the Bowman’s space surface area fraction [(A-B)/A], where A denotes total glomerular area and B the glomerular tuft area. Hepatic ET-1 and inflammatory markers (TNF-α, MCP-1) were analyzed by RNA expression. Blood pressure was measured noninvasively.
Results
In males, antagomiR-125b preserved the Bowman’s space surface area fraction (0.34±0.05 vs. 0.21±0.09 in SC, p=0.012; vs. 0.26±0.05 in miR-125b, p=0.041) and reduced creatinine (1.91±2.3 vs. 3.34±2.5 in SC, p=0.045; vs. 5.47±1.3 mg/dL in miR-125b, p=0.01). In females, no significant changes were observed in Bowman’s space fraction (0.31±0.08 vs. 0.31±0.06 in SC, p=0.4; vs. 0.31±0.08 in miR-125b, p=0.8) or creatinine (1.80±1.2 vs. vs. 2.77±1.8 in SC, p=0.1; vs. 3.65±2.2 mg/dL in miR-125b,mg/dL; p=0.09).
AntagomiR-125b reduced TNF-α (p=0.008) and MCP-1 (p=0.004) expression in both sexes. However, it also increased ET-1 expression by 2.93-fold overall, with a more pronounced rise in females (3.93±3.2) than in antagomiR-125b-treated males (1.48±1.3).
In males, antagomiR-125b significantly reduced systolic and diastolic blood pressure (p=0.01). In contrast, females remained hypertensive, with systolic blood pressure of 149.6±13.9 mmHg, diastolic blood pressure of 115.6±12.8 mmHg, and mean arterial pressure of 126.3±13.2 mmHg; this hemodynamic profile was associated with persistent glomerular tuft crowding.
Conclusion
miR-125b inhibition induces sex-divergent renal effects by uncoupling inflammation from hemodynamic control. Despite reduced inflammation in both sexes, enhanced ET-1–mediated vasoconstriction sustains hypertension in females and limits renal protection. These findings identify the miR-125b/ET-1 axis as a sex-specific therapeutic target in hypertensive kidney disease.
Acknowledgment
This study has been funded by the Instituto de Salud Carlos III (Co-funded by the European Regional Development Fund (ERDF), a way to build Europe) through the project PI 23/00927 (to M.H).
Funding
- Government Support – Non-U.S.