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Updated: Jul 5, 2025
Analyses of Proteinuria, Renal Infiltration of Leukocytes, and Renal Deposition of Proteins in Lupus-prone MRL/lpr Mice
Published on: June 8, 2022
Circulating exosomal microRNAs as biomarkers of lupus nephritis
Fei Chen1, Bo Shi1, Wenjing Liu1
1Department of Clinical Laboratory, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Objective:
Disruption in the delicate symphony of genes, microRNA (miRNA), or protein expression can result in the dysregulation of the immune system, leading to the devastating consequences such as lupus nephritis (LN). The capacity of exosomes to transport miRNAs between cells and modify the phenotype of recipient cells implies their involvement in persistent kidney inflammation. This study unveils identifying two previously undiscovered exosomal miRNAs in the serum of LN patients, offering potential solutions to the current challenges in LN diagnosis and management.
Methods:
Initially, we used a reagent-based kit to isolate serum exosomes from patients with Systemic lupus erythematosus (SLE) and used Trizol method for total RNA extraction. Subsequently, we employed small RNA sequencing to screen for differential expression profiles of exosomal small RNAs. The RT-qPCR method was used to individually validate samples in both the screening and validation cohorts, enabling the identification of candidate small RNAs; specific to LN. We assessed the diagnostic potency using receiver operating characteristic (ROC) curve, and explored the biological roles of miRNAs using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses.
Results:
Compared to SLE patients without LN, SLE patients accompanied by LN exhibited significantly spiked levels of exosomal hsa-miR-4796-5p and hsa-miR-7974. The duo of miRNAs, hsa-miR-4796-5p and hsa-miR-7974, exhibited promising potential as biomarkers for diagnosing LN, with an AUC exceeding 0.8. Correlation analysis revealed a strong positive association between these miRNAs and proteinuria, as well as the SLE Disease Activity Index (SLEDAI) score. Moreover, the levels of two miRNAs in LN patients were significantly elevated in comparison to other autoimmune nephritis conditions, such as immunoglobulin A nephropathy (IgAN) and diabetic nephropathy (DN). Furthermore, the bioinformatics analysis indicated that this miRNAs duo can play a pivotal role in the regulation of immune processes by modulating signal pathways, such as the mTOR and PI3K-Akt signaling pathway.
Conclusion:
This study provides a new ground that serum exosomal miRNAs can effectively identify and predict LN in SLE patients.
Insights
Researchers identified two novel exosomal microRNAs (miRNAs) in lupus nephritis (LN) patients
Area of Science:
- Immunology
- Genetics
- Biochemistry
Background:
- Immune system dysregulation, driven by genetic or molecular disruptions, can lead to conditions like lupus nephritis (LN).
- Exosomes, carrying microRNAs (miRNAs), play a role in cell-to-cell communication and may contribute to persistent kidney inflammation in LN.
- Current diagnostic and management strategies for LN face challenges, highlighting the need for novel biomarkers.
Purpose of the Study:
- To identify novel exosomal microRNAs (miRNAs) in the serum of lupus nephritis (LN) patients.
- To evaluate the diagnostic potential of these identified exosomal miRNAs as biomarkers for LN.
- To explore the biological functions and signaling pathways associated with these candidate miRNAs.
Main Methods:
- Serum exosomes were isolated from patients with Systemic Lupus Erythematosus (SLE) with and without LN.
- Small RNA sequencing was performed to screen for differentially expressed exosomal small RNAs.
- RT-qPCR was used for validation, and Receiver Operating Characteristic (ROC) curve analysis assessed diagnostic accuracy.
- Bioinformatics analyses (GO and KEGG) were employed to predict the biological roles of the identified miRNAs.
Main Results:
- Two exosomal miRNAs, hsa-miR-4796-5p and hsa-miR-7974, were significantly elevated in SLE patients with LN compared to those without LN.
- These miRNAs demonstrated promising diagnostic potential for LN, with an Area Under the Curve (AUC) exceeding 0.8.
- Elevated levels of these miRNAs correlated positively with proteinuria and SLE Disease Activity Index (SLEDAI) scores.
- The identified miRNAs were also significantly higher in LN patients compared to those with IgA nephropathy (IgAN) and diabetic nephropathy (DN).
- Bioinformatics analysis suggested these miRNAs regulate immune processes via pathways like mTOR and PI3K-Akt signaling.
Conclusions:
- Serum exosomal miRNAs, specifically hsa-miR-4796-5p and hsa-miR-7974, can serve as effective biomarkers for the identification and prediction of LN in SLE patients.
- These findings offer a potential new avenue for improving LN diagnosis and management.
- The study underscores the role of exosomal miRNAs in the pathogenesis of lupus nephritis.
