Improvement of membranous nephropathy by inhibition of miR‐193a to affect podocytosis via targeting WT1

Abstract

The objective of this paper was to explore the role and molecular mechanism of miR-193a in membranous nephropathy (MN). Experimental rats and podocytes were randomly divided into four groups: control, MN, miR-NC, and miR-193a inhibitor groups. The relative mRNA level of miR-193a was determined. The mRNA level and protein expression of PODXL, NPHS1, and Notch1 were determined by real-time polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. The mRNA level and protein expression of WT1 in podocytes were also determined by RT-PCR and Western blot analysis. The relative mRNA level of miR-193a in the MN group was significantly higher than that in the control group, and inhibition of miR-193a inhibited the increase successfully. Inhibition of miR-193a inhibited renal injury, podocyte injury, and tissue cell apoptosis resulting from MN. The expression of PODXL, NPHS1, and Notch1 was decreased in the MN group, while the expression was increased in the miR-193a inhibitor group. WT1 was verified as a target gene of miR-193a and the expression of WT1 increased after inhibition of miR-193a. Inhibition of miR-193a by targeting WT1 could inhibit renal function injury, renal tissue cell apoptosis, and podocytosis. K E Y W O R D S membranous nephropathy (MN), miR-193a, podocyte, renal function, WT1 J Cell Biochem. 2019;120:3438-3446. wileyonlinelibrary.com/journal/jcb 3438 |

Serum Protein Signatures Using Aptamer-Based Proteomics for Minimal Change Disease and Membranous Nephropathy

“…30 Increased apoptosis in MN was another hallmark observed in our protein signature data and is consistent with glomerular injury that results in cell death and loss of podocytes. 31,32 In contrast, MCD generally displayed a different immune profile and reduced cell death but enhanced vascular functions compared with MN. For example, several proteins involved in adaptive immunity were dysregulated in MCD, including CD40LG, CSF1, TNFRSF17, CCL21, and STAT1/3, in keeping with the proposed disease pathogenesis that involves T and B lymphocytes.…”

Fumarate modulates phospholipase A2 receptor autoimmunity-induced podocyte injury in membranous nephropathy

“…16 A recent study demonstrated that the phenotypic change of podocytes might also be induced by the deletion of WT1, 27 which is required for maintaining the differentiated phenotype during podocyte injury in proteinuric kidney diseases, such as diabetic nephropathy and MN. 28,29 Interestingly, the inhibition of FH activity and the subsequent accumulation of fumarate have been reported to trigger the change of phenotypic profile through the mechanism by which fumarate induces ROS by modifying glutathione metabolism or ROS-related-miRNAs. 21,22,30 In the present study, we demonstrated that the podocytes in the milieu of PLA2R-associated MN lose their epithelial and differentiation markers accompanied by the acquisition of mesenchymal features.…”

MicroRNA‑193a‑5p exerts a tumor suppressive role in epithelial ovarian cancer by modulating RBBP6

“…For example, miR-193a-5p expression levels are downregulated in numerous types of cancer, including colon cancer, non-small cell lung cancer, human endometrioid endometrial adenocarcinoma and prostate cancer, which has been reported to be associated with tumor progression (18)(19)(20)26,27). A previous study also reported an improvement to membranous nephropathy following miR-193a inhibition, which affected podocytosis by targeting WT1 transcription factor (WT1) (28). Jin et al (29) demonstrated that miR-193a-5p exerted a tumor-suppressive role in glioblastoma via modulating NOVA alternative splicing regulator 1.…”