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Investigation of MicroRNA in Mitochondrial Apoptotic Pathway in Systemic Lupus Erythematosus
Yu-Jih Su1, Nai-Wen Tsai2, Chia-Te Kung3
1Department of Rheumatology, Allergy and Immunology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
Background:
Accumulating evidence indicates that microRNAs play a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE). This study tested the hypothesis that microRNA is associated with the mitochondrial apoptotic pathway in patients with SLE.
Methods:
Thirteen patients were in the clinical comparison study and microRNA study and overall 19 patients in the study of intracellular protein. Levels of microRNAs were determined by miRNeasy kit in 13 patients with SLE and 29 volunteer normal controls. Intracellular levels of caspase-9, caspase-10, MAVS, MDA5, and pIRF7 in mononuclear cells from 19 patiens and the SLE disease activity index (SLEDAI) were determined in all SLE patients. Correlation analyses were performed among microRNAs, intracellular adaptor proteins, and caspase levels and mean SLEDAI.
Results:
The ΔCT, defined by test reading difference between the target and the internal control microRNA (miR-451a), of miR-21-5p, miR-150-5p, and miR221-3p were significantly higher in plasma from SLE patients than in normal controls. miR-150-5pΔCT was positively correlated with both CRP and SLEDAI value. miR-150-5pΔCT was negatively associated with MAVS 70 kD. Caspase-10 protein levels were negatively associated with plasma miR-22-3pΔCT and miR-21-5pΔCT levels.
Conclusions:
Our study confirmed the hypothesis that these microRNAs were associated with the mitochondrial apoptotic pathway in SLE. miR-150-5pΔCT was positively associated with SLE disease activity and it was negatively correlated with MAVS 70 kD, which may facilitate viral survival and further enhance inflammation. On the other hand, miR-22-3pΔCT and miR-21-5pΔCT, were negatively correlated with caspase-10 levels, which may repress extrinsic apoptosis and increase cell survival.
Insights
This study reveals that specific microRNAs are linked to the mitochondrial apoptotic pathway in systemic lupus erythematosus (SLE). Elevated levels of certain microRNAs correlate with SLE disease activity and influence apoptosis, offering new insights into SLE pathogenesis.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- MicroRNAs are increasingly recognized for their role in the pathogenesis of systemic lupus erythematosus (SLE).
- This research investigates the association between microRNAs and the mitochondrial apoptotic pathway in SLE patients.
Purpose of the Study:
- To test the hypothesis that microRNAs are associated with the mitochondrial apoptotic pathway in patients with SLE.
- To explore the relationship between specific microRNAs, apoptosis-related proteins, and disease activity in SLE.
Main Methods:
- MicroRNA levels were quantified in 13 SLE patients and 29 healthy controls using the miRNeasy kit.
- Intracellular levels of apoptosis-related proteins (caspase-9, caspase-10) and adaptor proteins (MAVS, MDA5, pIRF7) were measured in 19 SLE patients.
- Correlation analyses were performed between microRNA levels, protein expression, and SLE disease activity index (SLEDAI).
Main Results:
- Plasma levels of miR-21-5p, miR-150-5p, and miR-221-3p were significantly higher in SLE patients compared to controls.
- miR-150-5p levels positively correlated with SLEDAI and C-reactive protein (CRP), and negatively with MAVS.
- miR-22-3p and miR-21-5p levels showed a negative association with caspase-10 protein levels.
Conclusions:
- The study confirms the association between specific microRNAs and the mitochondrial apoptotic pathway in SLE.
- miR-150-5p may promote viral survival and inflammation by negatively correlating with MAVS, thus increasing SLE disease activity.
- miR-22-3p and miR-21-5p may enhance cell survival in SLE by repressing extrinsic apoptosis through negative correlation with caspase-10.
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