MicroRNA-21 promotes the progression of peritoneal fibrosis through the activation of the TGF-β/Smad signaling pathway: An in vitro and in vivo study

Abstract

The present study aimed to explore the roles of microRNA-21 (miR‑21) and the transforming growth factor-β (TGF-β)/Smad signaling pathway in the development of peritoneal fibrosis (PF). First, dialysis effluents from 30 patients with PF were collected, and after the establishment of a mouse model of PF, hematoxylin and eosin (H&E) and Masson's staining were used to observe peritoneal tissues, inflammatory cells and blood vessels. High glucose was used to stimulate human peritoneal mesothelial cell lines and these stimulated cells were then transfected with miR‑21 inhibitor. Immunofluorescence microscopy was applied for the observation of the transfected cells. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of miR‑21, and RT-qPCR and western blot analysis were used to detect the mRNA and protein expression of Zonula occludens-1 (ZO-1), TGF-β, Smad, vimentin and connective-tissue growth factor (CTGF). The mRNA and protein expression levels TGF-β, Smad-3, vimentin and CTGF were elevated, while ZO-1 mRNA and protein expression was decreased with the prolonged duration of dialysis treatment in the patients with PF. The experiments using the mouse model of PF revealed that the peritoneal connective tissue was thickened, while the numbers of inflammatory cells and blood vessels were increased. The expression levels of miR‑21, and the mRNA and protein expression levels of TGF-β, Smad-3, vimentin and CTGF were increased over time, whereas the mRNA and protein expression levels ZO-1 constantly decreased in the mice in the experimental group. Moreoever, the expression of miR‑21 positively correlated with the expression levels of TGF-β, Smad-3, vimentin and CTGF, while it negatively correlated with the expression of ZO-1. The results of H&E and Masson's staining revealed that miR‑21 expression was associated with the degree of PF. These findings thus indicate that miR‑21 promotes the progression of PF through the activation of the TGF-β/Smad signaling pathway.

Total flavone of Abelmoschus manihot suppresses epithelial-mesenchymal transition via interfering transforming growth factor-β1 signaling in Crohn’s disease intestinal fibrosis

“…Blocking TGF-β/Smad signaling has become a hot spot to inhibit or even reverse fibrosis. It has been reported that silencing Smad 2/3 could block Smad signaling and reduce collagen synthesis and proliferation of fibroblasts[ 40 , 41 ]. We silenced the expression of p-Smad2/3 and explored the role of Smad2/3 in TGF-β1-treated IEC-6 cells.…”

MicroRNA-145 promotes the epithelial-mesenchymal transition in peritoneal dialysis-associated fibrosis by suppressing fibroblast growth factor 10

“…In addition, human umbilical cord mesenchymal stem cells facilitate the up-regulation of miR-153-3p, which is a critical molecule in attenuating methylglyoxal-induced peritoneal fibrosis in rats (13). Specifically, miR-21 was shown to promote the progression of peritoneal fibrosis through activating the TGF-␤/Smad signaling pathway in in vivo and in vitro experiments (14). In fact, miR-129-5p was reported to directly target the 3Ј-UTR of the Smad-interacting protein 1 (SIP1) and SRY-box 4 (SOX4) genes and repress their post-transcriptional activities to modulate the EMT and fibrosis in the setting of PD (15).…”

Extracellular vesicles released by melanocytes after UVA irradiation promote intercellular signaling via miR21

“…The expression of the tumor suppressors PTEN and PDCD4 (Han et al, ; Peacock et al, ) is diminished, both in keratinocyte culture and in the ex vivo skin model. In line with these results, Ma et al showed that miR21‐null keratinocytes specifically upregulated SPRY1, PTEN, and PDCD4, which coincided with reduced phosphorylation of several effectors of the MAPK pathway including ERK, AKT, and JNK, stressing the miR21‐dependent regulation in the pathways (Ma, Chen, Yang, Chen, & Shi, ).…”