Downregulation of miR-137 Facilitates CD4+ T Cell Pyroptosis in Systemic Lupus Erythematosus via Stimulating AMPK Pathway

Autor: Aimin Gong, Long Mi, Fangzhi Wei, Yanping Zhuang, Yitian Song, Chengdan Pan, Xuan Zhang, Guiling Lin, Zhiquan Wu, Ying Liu
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Journal of Immunology Research, Vol 2023 (2023)
Druh dokumentu: article
ISSN: 2314-7156
DOI: 10.1155/2023/1241774
Popis: Objective. From the pathogenic mechanism point of view, systemic lupus erythematosus (SLE) features prominently in T lymphocyte apoptosis. Yet the regulatory mechanism underlying SLE cell apoptosis remains to be explored. This research intends to clarify the role played by miR-137 in SLE and the underlying mechanisms. Methods. Twenty SLE patients (SLE group) and twenty healthy controls (control group) were selected, from whom peripheral blood CD4+ T cells were isolated via magnetic-activated cell sorting. Reverse transcription-polymerase chain reaction (RT-PCR) quantified miR-137 and AMP-activated protein kinase (AMPK) in CD4+ T cells. Further, transfection of miR-137 mimics and inhibitors into CD4+ T cells was carried out to alter miR levels. Levels of pyroptosis, apoptosis, and inflammatory- and pyroptosis-related proteins were determined through PI staining, flow cytometry, and Western blotting, respectively. A luciferase reporter gene assay identified the targeting relation between miR-137 and AMPK. Results. SLE patients showed downregulated miR-137 and upregulated AMPK in CD4+ T cells than controls. miR-137 upregulation by miR-137 mimic transfection inhibited Jurkat cell pyroptosis and apoptosis at both mRNA and protein levels and suppressed NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome activity and pyroptosis-related protein gasdermin D (GSDMD), while miR-137 inhibitor transfection contributed to completely opposite effects. miR-137 directly targeted AMPK, as indicated by the luciferase reporter gene assay. Furthermore, miR-137 inhibitor intervention induced healthy CD4+ T cell pyroptosis and apoptosis via mediating AMPK, whereas miR-137 mimic transfection into CD4+ T cells of SLE patients leads to opposite results. Conclusion. Upregulating miR-137 inhibits CD4+ T cell pyroptosis in SLE patients by modulating the AMPK pathway, suggesting the potential diagnostic and therapeutic role of miR-137 in SLE.
Databáze: Directory of Open Access Journals
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