NEPHROLOGY / RESEARCH PAPER
Ox-low density lipoprotein (ox-LDL) increased the susceptibility of primary nephrotic syndrome (PNS) by regulating the Treg/Th17 ratio via the MEG3 signaling
Li Jin 1
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The First Affiliated Hospital of Xi'an Jiaotong University, China
CORRESPONDING AUTHOR
Shifeng Yang   

The First Affiliated Hospital of Xi'an Jiaotong University, China
Submission date: 2020-06-26
Final revision date: 2021-02-04
Acceptance date: 2021-02-27
Online publication date: 2021-03-20
 
 
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ABSTRACT
Introduction:
Patients with primary nephrotic syndrome (PNS) were reported to exhibit the 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:
40 PNS patients and 42 healthy individuals were recruited in this study. FCM assay was used to observe the levels of Treg and Th17 cells.

Results:
The Treg/Th17 ratio was evidently decreased in PNS patients. The levels of MEG3 and RORγt 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-1β were highly increased in PNS patients. Ox-low density lipoprotein (ox-LDL) treatment significantly increased the levels of MEG3 and RORγt 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 in 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 RORγt 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 signaling. The activation of MEG3/miR-125a/FOXP3 axis and MEG3/miR-17/RORγt axis respectively lead to the Treg/Th17 imbalance, which resulted in up-regulated IL-6 and IL-1β levels, thus increasing the susceptibility of PNS.

eISSN:1896-9151
ISSN:1734-1922