MiR-100-3p and miR-877-3p regulate overproduction of IL-8 and IL-1β in mesangial cells activated by secretory IgA from IgA nephropathy patients

Exp Cell Res. 2016 Oct 1;347(2):312-21. doi: 10.1016/j.yexcr.2016.08.011. Epub 2016 Aug 16.

Abstract

IgA nephropathy (IgAN) is the most common type of primary glomerulonephritis, characterized by mesangial deposition of pathogenic IgA and the injury to mesangial cells. Our previous studies indicate that secretory IgA (SIgA) plays an important role in the pathogenesis of IgAN, and miR-16 is involved in destructive process in mesangial cells mediated by the SIgA from IgAN patients. Our current study aimed to study the role of miRNAs in the effect of SIgA from IgAN patients on mesangial cells. MicroRNA microarray and cytokines assay were performed to obtain the differential microRNAs expression profile in human renal mesangial cells stimulated by SIgA from IgAN patients (P-SIgA) with the cells treated by SIgA from healthy subjects (N-SgA) as control. The microRNAs with the most significant differences in microarray analysis were validated by quantitative RT-PCR. Among them, miR-100-3p and miR-877-3p were selected to predict target gene related to cytokines detecting in this study. Fifty-six differentially expressed microRNAs were chosen and 17 microRNAs with the most prominent changes were validated. Compared with N-SIgA, P-SIgA increased the production of interleukin (IL)-1β, IL-8, monocyte chemotactic protein-1 and transforming growth factor-β1. In addition, we for the first time demonstrated that over-production of IL-8 induced by the SIgA was regulated by down-expression of miR-100-3p in mesangial cells. Similarly, IL-1β over-production was regulated by down-expression of miR-877-3p. Our findings represent a pathogenic microRNAs expression profiling in human mesangial cells activated by P-SIgA. Furthermore, we provide a new explanation characterizing the molecular mechanism responsible for the regulation of IL-1β and IL-8 production in P-SIgA-triggered mesangial cells.

Keywords: IgA nephropathy; Mesangial cells; MiR-100-3p; MiR-877-3p; Secretory IgA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Base Sequence
  • Case-Control Studies
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Demography
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Glomerulonephritis, IGA / genetics*
  • Glomerulonephritis, IGA / pathology
  • Humans
  • Immunoglobulin A, Secretory / metabolism*
  • Interleukin-1beta / biosynthesis*
  • Interleukin-8 / biosynthesis*
  • Mesangial Cells / metabolism*
  • Mesangial Cells / pathology
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Real-Time Polymerase Chain Reaction
  • Reproducibility of Results
  • Young Adult

Substances

  • Cytokines
  • Immunoglobulin A, Secretory
  • Interleukin-1beta
  • Interleukin-8
  • MIRN100 microRNA, human
  • MIRN877 microRNA, human
  • MicroRNAs