Exosomes derived let-7f-5p is a potential biomarker of SLE with anti-inflammatory function

Area of Science:

• Immunology
• Molecular Biology
• Genetics

Background:

• Systemic lupus erythematosus (SLE) is a complex autoimmune disease with poorly understood molecular mechanisms.
• MicroRNAs (miRNAs) play crucial roles in regulating gene expression and are implicated in various autoimmune conditions.
• Aberrant expression of specific miRNAs may contribute to SLE pathogenesis and inflammation.

Purpose of the Study:

• To investigate the role of microRNA let-7f-5p in the pathogenesis of systemic lupus erythematosus (SLE).
• To identify potential molecular targets and pathways regulated by let-7f-5p in SLE.
• To explore the clinical utility of let-7f-5p as a biomarker for SLE and associated inflammation.

Main Methods:

• Analysis of let-7f-5p expression in peripheral blood mononuclear cells of SLE patients.
• High-throughput RNA sequencing and bioinformatics analysis of renal tissue exosomes from SLE-prone mice.
• In vitro studies using macrophage inflammation models and mesenchymal stem cell co-cultures.
• Dual luciferase reporter gene assays to confirm direct miRNA-target interactions.

Main Results:

• Significantly downregulated expression of let-7f-5p was observed in SLE patients and in renal exosomes of SLE-prone mice.
• Upregulation of guanylate binding proteins (Gbp2 and Gbp7) correlated with decreased let-7f-5p levels in inflamed macrophages.
• Transfection with a let-7f-5p mimic alleviated macrophage inflammation and downregulated Gbp2 and Gbp7 expression.
• let-7f-5p was confirmed to directly bind to the 3' UTR of Gbp7, regulating its expression.

Conclusions:

• let-7f-5p dysregulation is implicated in the pathogenesis of SLE.
• The let-7f-5p-Gbp family axis plays a role in regulating macrophage inflammation in SLE.
• let-7f-5p represents a potential biomarker for SLE and associated inflammatory responses with possible clinical applications.