MiR-454-3p regulates high glucose-induced mesothelial-mesenchymal transition and glycolysis in peritoneal mesothelial cells by targeting STAT3

Background The quality of life of patients receiving long-term peritoneal dialysis (PD) is significantly impacted by the onset of peritoneal fibrosis (PF), and one of the pathological changes is mesothelial-mesenchymal transition (MMT). In this study, we investigated the potential roles of miR-454-3...

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Main Authors: Nan Li, Jiao Fu, Qiufeng Wang, Qingqing Rao, Ling Yao, Xiaoqi Shao, Pei Zhang
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Renal Failure
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Online Access:https://www.tandfonline.com/doi/10.1080/0886022X.2024.2394635
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author Nan Li
Jiao Fu
Qiufeng Wang
Qingqing Rao
Ling Yao
Xiaoqi Shao
Pei Zhang
author_facet Nan Li
Jiao Fu
Qiufeng Wang
Qingqing Rao
Ling Yao
Xiaoqi Shao
Pei Zhang
author_sort Nan Li
collection DOAJ
description Background The quality of life of patients receiving long-term peritoneal dialysis (PD) is significantly impacted by the onset of peritoneal fibrosis (PF), and one of the pathological changes is mesothelial-mesenchymal transition (MMT). In this study, we investigated the potential roles of miR-454-3p and signal transducer and activator of transcription 3 (STAT3) in the progression of peritoneal MMT and the underlying mechanisms.Methods Peritoneums were collected to detect morphology via hematoxylin-eosin staining and differentially expressed miRNAs were detected via RT-qPCR. PD effluent-derived cell populations in the peritoneal cavity were isolated from the effluents of 20 PD patients to determine miR-454-3p, STAT3, and MMT markers via Western blotting and RT-qPCR. The relationship between miR-454-3p and STAT3 was examined via a dual-luciferase reporter assay. Western blotting and RT-qPCR were utilized to evaluate the expression of STAT3, MMT markers, and glycolytic enzymes. Immunofluorescence staining revealed the localization and expression of MMT markers and STAT3.Results MiR-454-3p was downregulated in the peritoneums and PD effluent-derived cell populations of long-term PD patients. High glucose (HG) treatment promoted HMrSV5 cell MMT and glycolysis. MiR-454-3p overexpression alleviated HG-induced MMT and suppressed the expression of STAT3 and glycolytic enzymes. In contrast, the miR-454-3p inhibitor exacerbated HG-induced MMT and promoted the expression of glycolytic enzymes and STAT3. Moreover, STAT3 was the target of miR-454-3p.Conclusions This study demonstrated the protective role of miR-454-3p in HG-induced MMT and glycolysis in HMrSv5 cells, suggesting that miR-454-3p may prevent MMT by suppressing glycolytic enzymes via the STAT3/PFKFB3 pathway in the HG environment.
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series Renal Failure
spelling doaj-art-a0efa9c2ceb74c4c88a8eed71e492d8e2025-08-20T03:12:50ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492024-12-0146210.1080/0886022X.2024.2394635MiR-454-3p regulates high glucose-induced mesothelial-mesenchymal transition and glycolysis in peritoneal mesothelial cells by targeting STAT3Nan Li0Jiao Fu1Qiufeng Wang2Qingqing Rao3Ling Yao4Xiaoqi Shao5Pei Zhang6Department of Nephropathy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, ChinaDepartment of Nephropathy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, ChinaDepartment of Nephropathy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, ChinaDepartment of Nephropathy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, ChinaDepartment of Nephropathy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, ChinaDepartment of Nephropathy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, ChinaDepartment of Nephropathy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, ChinaBackground The quality of life of patients receiving long-term peritoneal dialysis (PD) is significantly impacted by the onset of peritoneal fibrosis (PF), and one of the pathological changes is mesothelial-mesenchymal transition (MMT). In this study, we investigated the potential roles of miR-454-3p and signal transducer and activator of transcription 3 (STAT3) in the progression of peritoneal MMT and the underlying mechanisms.Methods Peritoneums were collected to detect morphology via hematoxylin-eosin staining and differentially expressed miRNAs were detected via RT-qPCR. PD effluent-derived cell populations in the peritoneal cavity were isolated from the effluents of 20 PD patients to determine miR-454-3p, STAT3, and MMT markers via Western blotting and RT-qPCR. The relationship between miR-454-3p and STAT3 was examined via a dual-luciferase reporter assay. Western blotting and RT-qPCR were utilized to evaluate the expression of STAT3, MMT markers, and glycolytic enzymes. Immunofluorescence staining revealed the localization and expression of MMT markers and STAT3.Results MiR-454-3p was downregulated in the peritoneums and PD effluent-derived cell populations of long-term PD patients. High glucose (HG) treatment promoted HMrSV5 cell MMT and glycolysis. MiR-454-3p overexpression alleviated HG-induced MMT and suppressed the expression of STAT3 and glycolytic enzymes. In contrast, the miR-454-3p inhibitor exacerbated HG-induced MMT and promoted the expression of glycolytic enzymes and STAT3. Moreover, STAT3 was the target of miR-454-3p.Conclusions This study demonstrated the protective role of miR-454-3p in HG-induced MMT and glycolysis in HMrSv5 cells, suggesting that miR-454-3p may prevent MMT by suppressing glycolytic enzymes via the STAT3/PFKFB3 pathway in the HG environment.https://www.tandfonline.com/doi/10.1080/0886022X.2024.2394635Glycolysismesothelial-mesenchymal transition (MMT)miR-454-3pperitoneal fibrosisSTAT3
spellingShingle Nan Li
Jiao Fu
Qiufeng Wang
Qingqing Rao
Ling Yao
Xiaoqi Shao
Pei Zhang
MiR-454-3p regulates high glucose-induced mesothelial-mesenchymal transition and glycolysis in peritoneal mesothelial cells by targeting STAT3
Renal Failure
Glycolysis
mesothelial-mesenchymal transition (MMT)
miR-454-3p
peritoneal fibrosis
STAT3
title MiR-454-3p regulates high glucose-induced mesothelial-mesenchymal transition and glycolysis in peritoneal mesothelial cells by targeting STAT3
title_full MiR-454-3p regulates high glucose-induced mesothelial-mesenchymal transition and glycolysis in peritoneal mesothelial cells by targeting STAT3
title_fullStr MiR-454-3p regulates high glucose-induced mesothelial-mesenchymal transition and glycolysis in peritoneal mesothelial cells by targeting STAT3
title_full_unstemmed MiR-454-3p regulates high glucose-induced mesothelial-mesenchymal transition and glycolysis in peritoneal mesothelial cells by targeting STAT3
title_short MiR-454-3p regulates high glucose-induced mesothelial-mesenchymal transition and glycolysis in peritoneal mesothelial cells by targeting STAT3
title_sort mir 454 3p regulates high glucose induced mesothelial mesenchymal transition and glycolysis in peritoneal mesothelial cells by targeting stat3
topic Glycolysis
mesothelial-mesenchymal transition (MMT)
miR-454-3p
peritoneal fibrosis
STAT3
url https://www.tandfonline.com/doi/10.1080/0886022X.2024.2394635
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