MicroRNA-21 promotes the progression of peritoneal fibrosis through the activation of the TGF-ß/Smad signaling pathway: An in vitro and in vivo study.
Int J Mol Med
; 41(2): 1030-1038, 2018 Feb.
Article
en En
| MEDLINE
| ID: mdl-29207016
ABSTRACT
The present study aimed to explore the roles of microRNA-21 (miR21) and the transforming growth factor-ß (TGF-ß)/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 miR21 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 miR21, and RT-qPCR and western blot analysis were used to detect the mRNA and protein expression of Zonula occludens-1 (ZO-1), TGF-ß, Smad, vimentin and connective-tissue growth factor (CTGF). The mRNA and protein expression levels TGF-ß, 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 miR21, and the mRNA and protein expression levels of TGF-ß, 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 miR21 positively correlated with the expression levels of TGF-ß, 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 miR21 expression was associated with the degree of PF. These findings thus indicate that miR21 promotes the progression of PF through the activation of the TGF-ß/Smad signaling pathway.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Peritoneo
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MicroARNs
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Fibrosis Peritoneal
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Int J Mol Med
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Año:
2018
Tipo del documento:
Article