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Hsa-miR-3202 attenuates Jurkat cell infiltration via MMP2 in primary Sjögren's syndrome
1Department of Rheumatology and Immunology, The First Hospital of Jilin University, Changchun, China.
Background:
Primary Sjögren's syndrome is characterized by lymphocytic infiltration and dysfunction of exocrine glands. The persistent presence of lymphocytes in these glands is an important cause of injury to glandular epithelial cells. MicroRNAs play an important role in primary Sjögren's syndrome and regulate mRNA expression. This study evaluated the expression of microRNA related to lymphocyte infiltration in primary Sjögren's syndrome patients so as to find novel diagnostic and therapeutic targets for primary Sjögren's syndrome. We also explored the microRNA-mRNA networks related to lymphocyte infiltration.
Methods:
mRNA-seq and microRNA-seq of peripheral blood mononuclear cells (PBMCs) were performed on samples from five primary Sjögren's syndrome patients and five matched healthy controls. Meanwhile, microRNA-mRNA network analysis was also conducted. RT-qPCR was used for validation of differentially expressed RNAs. Immunohistochemistry analysis was used to detect MMP2 expression in labial gland tissue. Hsa-miR-3202 mimics/inhibitor-transfected Jurkat cells were used to measure the effects of hsa-miR-3202 on the infiltration potential of T cells.
Results:
mRNA and microRNA sequencing revealed that 84 differentially expressed mRNAs and 49 differentially expressed microRNAs had a mutual regulatory relationship. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that differentially expressed MMP2 and its related microRNA, hsa-miR-3202, were enriched in the leukocyte transendothelial migration pathway. MMP2 was highly expressed in PBMC and labial gland tissue in primary Sjögren's syndrome patients. Hsa-miR-3202 was lower expressed in primary Sjögren's syndrome than healthy control. Furthermore, hsa-miR-3202 mimics transfection decreased MMP2 expression in Jurkat cells, and inhibited Jurkat cells invasion (p = 0.047).
Conclusion:
Large number of differentially expressed microRNAs and mRNAs were detected in primary Sjögren's syndrome, and these differentially expressed microRNAs and mRNAs had a mutual regulatory relationship and played an important role in primary Sjögren's syndrome. In the study, we found hsa-miR-3202 regulate MMP2 and inhibited the infiltration of T cells from peripheral blood into the gland, which played a protective role.
Insights
MicroRNA hsa-miR-3202 regulates MMP2, inhibiting T cell infiltration in primary Sjögren's syndrome. This finding offers potential diagnostic and therapeutic targets for this autoimmune condition.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Primary Sjögren's syndrome involves lymphocytic infiltration and exocrine gland dysfunction.
- MicroRNAs are key regulators of gene expression implicated in Sjögren's pathogenesis.
- Understanding microRNA's role in lymphocyte infiltration is crucial for identifying therapeutic targets.
Purpose of the Study:
- To evaluate microRNA expression related to lymphocyte infiltration in primary Sjögren's syndrome.
- To identify novel diagnostic and therapeutic targets for primary Sjögren's syndrome.
- To explore microRNA-mRNA networks associated with lymphocyte infiltration.
Main Methods:
- RNA sequencing (mRNA-seq and microRNA-seq) on peripheral blood mononuclear cells (PBMCs) from patients and controls.
- MicroRNA-mRNA network analysis and RT-qPCR validation.
- Immunohistochemistry and cell-based assays to assess MMP2 and hsa-miR-3202 function in T cell infiltration.
Main Results:
- Identified 84 differentially expressed mRNAs and 49 microRNAs with mutual regulatory relationships.
- Found enrichment of MMP2 and hsa-miR-3202 in the leukocyte transendothelial migration pathway.
- Observed high MMP2 and low hsa-miR-3202 expression in primary Sjögren's syndrome; hsa-miR-3202 mimics reduced MMP2 and T cell invasion.
Conclusions:
- Significant microRNA-mRNA dysregulation occurs in primary Sjögren's syndrome, impacting lymphocyte infiltration.
- Hsa-miR-3202 regulates MMP2, inhibiting T cell infiltration and potentially offering a protective role.
- These findings highlight hsa-miR-3202 as a promising therapeutic target for primary Sjögren's syndrome.
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