Skip to main content
. 2021 Jan 25;8:618536. doi: 10.3389/fcell.2020.618536

Figure 6.

Figure 6

miRNAs interfere with inflammation in DN by affecting interleukin 18 secretion. During the diabetic process, obesity and hyperglycaemia reduce the expression of miR-346 in the renal cortex. miR-346 binds to the 3′-UTR of Bruton's tyrosine kinase (Btk) mRNA to inhibit its transcription, leading to the downregulation of Btk protein. Therefore, the increased Btk stabilizes the mRNA of IL-18 to ensure its secretion and ultimately promotes the inflammatory response in diabetic kidneys. Moreover, high glucose and AGEs down-regulate the expression of miR-15a, miR-20b, and miR-181c. Among them, miR-20b targets the KLF10 gene to promote KLF10 mRNA transcription, which then binds to IL18 to mediate and accelerate the inflammatory response in renal endothelial cells. miR-130a and the miR-379/411 cluster elevate IL-18 to promote the release of IFN-γ, resulting in the production of other inflammatory cytokines, such as ICAM-1, and promoting endothelial cell apoptosis. These alterations are associated with glomerular and tubulointerstitial inflammation and eventually contribute to DN progression. BTK, bruton's tyrosine kinase; KLF10, kruppel-like factor 10; TXNIP, thioredoxin interaction protein.