Upregulated microRNAs in membranous glomerulonephropathy are associated with significant downregulation of IL6 and MYC mRNAs

Abstract

Membranous glomerulonephropathy (MGN) is a glomerulopathy characterized by subepithelial deposits of immune complexes on the extracapillary side of the glomerular basement membrane. Insertion of C5b‐9 (complement membrane‐attack complex) into the membrane leads to functional impairment of the glomerular capillary wall. Knowledge of the molecular pathogenesis of MGN is actually scanty. MicroRNA (miRNA) profiling in MGN and unaffected tissues was performed by TaqMan Low‐Density Arrays. Expression of miRNAs and miRNA targets was evaluated in Real‐Time polymerase chain reaction (PCR). In vitro transient silencing of miRNAs was achieved through transfection with miRNA inhibitors. Ten miRNAs (let‐7a‐5p, let‐7b‐5p, let‐7c‐5p, let‐7d‐5p, miR‐107, miR‐129‐3p, miR‐423‐5p, miR‐516‐3p, miR‐532‐3p, and miR‐1275) were differentially expressed (DE) in MGN biopsies compared to unaffected controls. Interleukin 6 (IL6) and MYC messenger RNAs (mRNAs; targets of DE miRNAs) were significantly downregulated in biopsies from MGN patients, and upregulated in A498 cells following let‐7a‐5p or let‐7c‐5p transient silencing. Gene ontology analysis showed that DE miRNAs regulate pathways associated with MGN pathogenesis, including cell cycle, proliferation, and apoptosis. A significant correlation between DE miRNAs and mRNAs and clinical parameters (i.e., antiphospholipid antibodies, serum creatinine, estimated glomerular filtration, proteinuria, and serum cholesterol) has been detected. Based on our data, we propose that DE miRNAs and their downstream network may be involved in MGN pathogenesis and could be considered as potential diagnostic biomarkers of MGN.

Expression and 7-day time course of circulating microRNAs in septic patients treated with nephrotoxic antibiotic agents

“…In another clinical study of patients with membranous glomerulopathy, miR-423-5p was upregulated, in addition to nine other miRNAs, and positively correlated with proteinuria, suggesting an association with worsening glomerular damage. Upregulation of miR-423-5p also has been observed in renal biopsy tissues from patients with membranous glomerulopathy, accompanied by a decrease in IL-6, in contrast with our current observations [ 37 ]. In an experimental sepsis study of Mu et al with lipopolysaccharide-induced acute respiratory distress syndrome in animals, miR-423-5p was significantly downregulated and the FOXA1 gene was upregulated with progression of inflammation and fibrosis [ 38 ] (Fig.…”

CircNAPEPLD is expressed in human and murine spermatozoa and physically interacts with oocyte miRNAs

“…TaqMan® Human MicroRNA Arrays v. 3.0 A and B (ThermoFisher Scientific, Waltham, MA USA) were used to amplify 754 miRNAs as previously described [79]. Briefly, 160 ng of total RNA were reverse transcribed through Megaplex™ RT Primers, Human Pool Set v3.0 (ThermoFisher Scientific) and then pre-amplified through Megaplex™ PreAmp Primers, Human Pool Set v. 3.0 (ThermoFisher Scientific), according to manufacturer's instructions.…”

The rs6505162 C>A polymorphism in themiRNA-423gene exhibits a protective element of coronary artery in a southern Chinese population with Kawasaki disease

“…(33) In membranous glomerulonephropathy upregulation of miRNA-423 had a certain significant association with down regulated IL6. (34)We found that the descending expression of the designated genes on proliferation and differentiation in myoblast was caused by the upregulated miR-423-5p suppressing the suppressor of fused homolog in expression. (35) In the polymorphism of pre-MIR423 rs6505162, genetic mutations, C to A transition, inhibited the function of HEC-1b cell proliferation and migratory.…”