miR-150 inhibitor ameliorates adriamycin-induced focal segmental glomerulosclerosis

Area of Science:

• Nephrology
• Molecular Biology
• Immunology

Background:

• Focal segmental glomerulosclerosis (FSGS) is a leading cause of adult nephrotic syndrome in the USA.
• Current treatment options for FSGS are limited, and its underlying mechanisms are not fully understood.
• Previous research indicated that elevated microRNA-150 (miR-150) in podocytes promotes fibrosis and reduces the antifibrotic protein SOCS1.

Purpose of the Study:

• To investigate if inhibiting miR-150 can alleviate glomerular injury in a mouse model of FSGS.
• To elucidate the mechanisms by which miR-150 inhibition impacts FSGS pathology.

Main Methods:

• Adriamycin-induced FSGS mouse model.
• Administration of FAM-labeled locked nucleic acid-anti-miR-150 (LNA-anti-miR-150) via subcutaneous injection.
• Assessment of renal miR-150 levels, proteinuria, albuminemia, lipemia, profibrotic proteins, inflammatory cytokines, SOCS1 expression, and T cell infiltration.
• Analysis of miR-150 localization in renal biopsies from FSGS patients.

Main Results:

• Renal miR-150 levels were increased in adriamycin-induced FSGS mice.
• LNA-anti-miR-150 effectively inhibited renal miR-150 without systemic toxicity.
• Treatment with LNA-anti-miR-150 ameliorated proteinuria, hypoalbuminemia, and hyperlipemia in FSGS mice.
• Inhibition of miR-150 reverted elevated profibrotic proteins and inflammatory cytokines, increased SOCS1, and reduced T cell infiltration.
• miR-150 was predominantly located in podocytes of FSGS patient kidneys.

Conclusions:

• Inhibition of renal miR-150 using LNA-anti-miR-150 shows promise as a therapeutic strategy for FSGS.
• The protective effects are likely mediated through anti-fibrotic and anti-inflammatory actions, including reduced T cell infiltration.
• Targeting miR-150 in podocytes represents a potential novel therapeutic approach for FSGS treatment.