Exosomes from high glucose-treated macrophages promote epithelial–mesenchymal transition of renal tubular epithelial cells via long non-coding RNAs

Abstract

Background Macrophages contribute to epithelial–mesenchymal transition (EMT) in diabetic nephropathy (DN). Exosomal long non-coding RNAs (lncRNAs) derived from macrophages play a major role in transmitting biological information, whereas related studies on DN are rare. Here we investigated the effects of exosomal lncRNAs from high glucose-treated macrophages on EMT. Methods High glucose-treated macrophage exosomes (HG-exos) were extracted by coprecipitation and stabilized. Then, mouse renal tubular epithelial cells were treated with HG-exos for 24 h. Expression of E-cadherin, α-smooth muscle actin (α-SMA), and fibronectin was detected by western blotting, qPCR, and immunofluorescence. High-throughput sequencing was then applied to analyze the bioinformatics of HG-exos. Results HG-exos inhibited the proliferation of tubular epithelial cells. Additionally, HG-exos markedly upregulated α-SMA and fibronectin expression and downregulated E-cadherin expression in tubular epithelial cells, indicating EMT induction. A total of 378 differentially expressed lncRNAs and 674 differentially expressed mRNAs were identified by high-throughput sequencing of HG-exos. Bioinformatics analysis and subsequent qPCR validation suggested 27 lncRNAs were enriched in the EMT-related MAPK pathway. Among them, ENSMUST00000181751.1, XR_001778608.1, and XR_880236.2 showed high homology with humans. Conclusion Exosomes from macrophages induce EMT in DN and lncRNAs in exosomes enriched in the MAPK signaling pathway may be the possible mechanism.

Circular RNA hsa_circ_0005519 contributes to acute kidney injury via sponging microRNA-98-5p

“…anti-CIRC was used for further research owing to its higher knockdown efficiency. The designed siRNA should specifically aim to hsa_circ_0005519, to avoid any interference with its linear host gene [ 16 ]. Notably, the siRNAs in this study showed no effects on expression of SNX13 mRNA (hsa_circ_0005519 host gene) (Fig.…”

4D label-free proteomic analysis of vitreous from patients with rhegmatogenous retinal detachment

“…The pathogenesis of proliferative vitreoretinopathy is closely related to the epithelial-mesenchymal transition in retinal pigment epithelium cells, which is characterized by the downregulation of E-cadherin and the upregulation of N-cadherin. After the epithelial-mesenchymal transition, the expression levels of E-cadherin and keratin were decreased, whereas the expression levels of α-smooth muscle actin (α-SMA) and fibronectin were increased [19][20] . Elevated expression of E-cadherin is reportedly sufficient to inhibit epithelial-mesenchymal transition and proliferation in retinal pigment epithelium cells; this inhibits transforming growth factor (TGF)-β1-induced apoptosis, thereby delaying RRD progression to proliferative vitreoretinopathy [21] .…”

Relationship between Macrophages and Tissue Microenvironments in Diabetic Kidneys

“…Moreover, macrophages have been identified as the main source of myofibroblasts via macrophage-myofibroblast transition, thereby promoting renal fibrosis [60]. It has also been shown that exosomes from high glucose-treated macrophages promote RTECs to switch to a more pro-fibrosis phenotype via releasing long non-coding RNAs [61]. However, the role of exosomes in mediating intercellular communication requires further investigation.…”

“…Exosomes from high glucose-treated macrophage promote RTECs to switch to a more pro-fibrosis phenotype via releasing long non-coding RNAs [61] 6. Potential Therapeutics for DN by Targeting Macrophages…”