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NEPHROLOGY / RESEARCH PAPER
Oxidized low-density lipoprotein increased susceptibility to primary nephrotic syndrome by regulating the Treg/Th17 ratio via MEG3 signalling
1
Department of Nephrology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
Submission date: 2020-06-26
Final revision date: 2021-02-04
Acceptance date: 2021-02-27
Online publication date: 2021-03-20
Publication date: 2026-07-06
Arch Med Sci 2026;22(3):1399-1410
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Patients with primary nephrotic syndrome (PNS) were reported to exhibit an evident imbalance between the number of Th17 and Treg cells in their peripheral blood monocytes (PBMCs), which might be the immunological basis of the disease.
Material and methods:
Forty PNS patients and 42 healthy individuals were recruited to this study. Flow cytometry assay was used to measure the levels of Treg and Th17 cells.
Results:
The Treg/Th17 ratio was evidently decreased in PNS patients. The levels of MEG3 and RORgt were increased in the PNS group, while the levels of miR-17, miR-125a and FOXP3 mRNA were reduced in the PNS group. Moreover, the levels of IL-6 and IL-1b were highly increased in PNS patients. Oxidized low-density lipoprotein (ox-LDL) treatment significantly increased the levels of MEG3 and RORgt mRNA/protein while decreasing the levels of miR-17, miR-125a, and FOXP3 mRNA/protein in THP-1 cells, and the transfection of MEG3 siRNA partly alleviated the dysregulation of the expression of MEG3, relevant miRNAs and relevant mRNAs induced by ox-LDL. Also, the expression of miR-17 and miR-125a was evidently decreased upon the successful transfection of MEG3, but the RORgt mRNA/protein levels were promoted while the FOXP3 mRNA/protein levels were inhibited.
Conclusions:
Our results demonstrated that ox-LDL could promote the inflammatory response of PNS by decreasing the Treg/Th17 ratio via activating the MEG3 signalling. The activation of the MEG3/miR-125a/FOXP3 axis and MEG3/miR-17/RORgt axis led to the Treg/Th17 imbalance, which resulted in up-regulated IL-6 and IL-1b levels, thus increasing the susceptibility to PNS.
Patients with primary nephrotic syndrome (PNS) were reported to exhibit an evident imbalance between the number of Th17 and Treg cells in their peripheral blood monocytes (PBMCs), which might be the immunological basis of the disease.
Material and methods:
Forty PNS patients and 42 healthy individuals were recruited to this study. Flow cytometry assay was used to measure the levels of Treg and Th17 cells.
Results:
The Treg/Th17 ratio was evidently decreased in PNS patients. The levels of MEG3 and RORgt were increased in the PNS group, while the levels of miR-17, miR-125a and FOXP3 mRNA were reduced in the PNS group. Moreover, the levels of IL-6 and IL-1b were highly increased in PNS patients. Oxidized low-density lipoprotein (ox-LDL) treatment significantly increased the levels of MEG3 and RORgt mRNA/protein while decreasing the levels of miR-17, miR-125a, and FOXP3 mRNA/protein in THP-1 cells, and the transfection of MEG3 siRNA partly alleviated the dysregulation of the expression of MEG3, relevant miRNAs and relevant mRNAs induced by ox-LDL. Also, the expression of miR-17 and miR-125a was evidently decreased upon the successful transfection of MEG3, but the RORgt mRNA/protein levels were promoted while the FOXP3 mRNA/protein levels were inhibited.
Conclusions:
Our results demonstrated that ox-LDL could promote the inflammatory response of PNS by decreasing the Treg/Th17 ratio via activating the MEG3 signalling. The activation of the MEG3/miR-125a/FOXP3 axis and MEG3/miR-17/RORgt axis led to the Treg/Th17 imbalance, which resulted in up-regulated IL-6 and IL-1b levels, thus increasing the susceptibility to PNS.
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| eISSN: | 1896-9151 |
| ISSN: | 1734-1922 |
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