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Updated: May 7, 2026
Detection of MicroRNA Expression in the Kidneys of Immunoglobulin A Nephropathic Mice
Published on: July 8, 2020
Cellular and urinary microRNA alterations in NZB/W mice with hydroxychloroquine or prednisone treatment
Cristen B Chafin1, Nicole L Regna, Sarah E Hammond
1Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, United States.
Abstract:
Determining alterations to disease-associated miRNAs induced by specific therapeutics may allow the use of tailored therapy in lupus. We determined miRNA alterations in female NZB/W lupus mice treated with hydroxychloroquine (HCQ) or prednisone (PRED) for 12 weeks beginning at 24 weeks-of-age. B cell, PBMC, and urinary miR-let-7a expression were decreased with HCQ or PRED treatment. HCQ or PRED treatment reduced miR-21 expression in mesangial cells, T cells, pDCs, PBMCs, and the urine. MiR-146a expression was reduced in mesangial cells with HCQ treatment and in pDCs with HCQ or PRED treatment. PRED treatment increased miR-155 expression in mesangial, B, and T cells and PBMCs yet decreased miR-155 expression in pDCs and the urine. In vitro studies confirmed that HCQ or PRED's anti-inflammatory actions are dependent on their ability to inhibit miRNA expression. Our studies indicate that lupus therapeutics may work, in part, by altering the expression of disease-associated miRNAs.
Insights
Hydroxychloroquine (HCQ) and prednisone (PRED) alter microRNA (miRNA) expression in lupus mouse models. These lupus therapeutics may function by modulating disease-associated miRNA levels, suggesting potential for targeted therapies.
Area of Science:
- Immunology
- Molecular Biology
- Pharmacology
Background:
- Systemic lupus erythematosus (SLE) is a complex autoimmune disease.
- MicroRNAs (miRNAs) play a role in regulating immune responses and are implicated in lupus pathogenesis.
- Understanding how SLE therapeutics affect miRNA expression is crucial for developing targeted treatments.
Purpose of the Study:
- To investigate the impact of hydroxychloroquine (HCQ) and prednisone (PRED) on disease-associated miRNA alterations in a murine model of lupus.
- To explore the potential mechanisms by which HCQ and PRED exert their anti-inflammatory effects in lupus.
Main Methods:
- Female NZB/W lupus mice were treated with HCQ or PRED for 12 weeks.
- miRNA expression levels were analyzed in various cell types (B cells, PBMCs, mesangial cells, T cells, pDCs) and urine.
- In vitro studies were conducted to confirm the effect of HCQ and PRED on miRNA expression and anti-inflammatory actions.
Main Results:
- Both HCQ and PRED treatments decreased the expression of miR-let-7a in B cells, PBMCs, and urine.
- miR-21 expression was reduced in multiple cell types and urine following HCQ or PRED treatment.
- MiR-146a expression was reduced in mesangial cells and pDCs, while miR-155 showed differential regulation by PRED in various cell types and urine.
- In vitro experiments supported that the anti-inflammatory effects of HCQ and PRED are linked to miRNA expression inhibition.
Conclusions:
- Lupus therapeutics like HCQ and PRED can significantly alter the expression of disease-associated miRNAs.
- These miRNA modulations may represent a key mechanism through which these drugs exert their therapeutic effects in lupus.
- The findings suggest that targeting miRNA alterations could be a strategy for personalized therapy in lupus.
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