scholarly journals RhoA/Rho-kinase triggers epithelial-mesenchymal transition in mesothelial cells and contributes to the pathogenesis of dialysis-related peritoneal fibrosis

Oncotarget ◽  
2018 ◽  
Vol 9 (18) ◽  
pp. 14397-14412 ◽  
Author(s):  
Qinglian Wang ◽  
Xiaowei Yang ◽  
Ying Xu ◽  
Zhenwei Shen ◽  
Hongxia Cheng ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Rho Kinase ◽  
Mesothelial Cells ◽  
Peritoneal Fibrosis ◽  
Mesenchymal Transition

scholarly journals MiR-30b is involved in methylglyoxal-induced epithelial-mesenchymal transition of peritoneal mesothelial cells in rats

2014 ◽  
Vol 19 (2) ◽  
Author(s):  
Hong Liu ◽  
Ning Zhang ◽  
Da Tian
Keyword(s):  
Mirna Expression ◽  
Epithelial Mesenchymal Transition ◽  
Degradation Products ◽  
Mesothelial Cells ◽  
Control Group ◽  
Peritoneal Fibrosis ◽  
Expression Array ◽  
Mesenchymal Transition ◽  
Peritoneal Mesothelial Cells

AbstractEpithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells (PMC) is a major contributor to the pathogenesis of peritoneal fibrosis. EMT is at least in part caused by repeated exposure to glucose degradation products (GDPs), such as methylglyoxal (MGO). MiRNA contributes greatly to the EMT of PMCs. In this study, we tried to profile whether differences exist between the peritoneal membrane (PM) miRNA expression seen in control rats and that seen in rats injected intraperitoneally with MGO. We assessed whether miR-30b has a possible role in MGO-induced EMT of PMCs in rats. Comparative miRNA expression array and real-time PCR analyses were conducted for the control group at the start of the experiment and for the MGO group after 1 and 2 weeks. During the second week, the MGO rats were treated with: a chemically modified antisense RNA oligonucleotide (ASO) complementary to the mature miR-30b (ASO group); an miR-30b mismatch control sequence (MIS group); or a citrate buffer (EMT group). Bioinformatic analyses indicated that the 3′ untranslated region (3′-UTR) of bone morphogenetic protein 7 (BMP7) mRNA did contain a putative binding site for miR-30b. We also tried to investigate whether miR-30b targeted BMP7 in vitro by transfection. Of the upregulated miRNAs, miR-30b expression demonstrated the greatest increase. The administration of miR-30b ASO for two weeks significantly reduced α-SMA excretion and upregulated E-cadherin and BMP-7 expression. Our in vitro study showed that miR-30b directly targeted and inhibited BMP7 by binding to its 3’-UTR. Our results revealed that miR-30b is involved in MGO-induced EMT of PMCs in rats.

scholarly journals miRNA589 Regulates Epithelial-Mesenchymal Transition in Human Peritoneal Mesothelial Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Ke Zhang ◽  
Hao Zhang ◽  
Xun Zhou ◽  
Wen-bin Tang ◽  
Li Xiao ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Mesothelial Cell ◽  
Mesothelial Cells ◽  
Control Group ◽  
Peritoneal Fibrosis ◽  
Mesenchymal Transition ◽  
Peritoneal Mesothelial Cells ◽  
Human Peritoneal Mesothelial Cells ◽  
E Cadherin

Background. microRNA (miRNA, miR) are thought to interact with multiple mRNAs which are involved in the EMT process. But the role of miRNAs in peritoneal fibrosis has remained unknown.Objective. To determine if miRNA589 regulates the EMT induced by TGFβ1 in human peritoneal mesothelial cell line (HMrSV5 cells).Methods. 1. Level of miR589 was detected in both human peritoneal mesothelial cells (HPMCs) isolated from continuous ambulatory peritoneal dialysis (CAPD) patients’ effluent and HMrSV5 cells treated with or without TGFβ1. 2. HMrSV5 cells were divided into three groups: control group, TGFβ1 group, and pre-miR-589+TGFβ1 group. The level of miRNA589 was determined by realtime PCR. The expressions of ZO-1, vimentin, and E-cadherin in HPMCs were detected, respectively.Results. Decreased level of miRNA589 was obtained in either HPMCs of long-term CAPD patients or HMrSV5 cells treated with TGFβ1. In vitro, TGFβ1 led to upregulation of vimentin and downregulation of ZO-1 as well as E-cadherin in HMrSV5 cells, which suggested EMT, was induced. The changes were accompanied with notably decreased level of miRNA589 in HMrSV5 cells treated with TGFβ1. Overexpression of miRNA589 by transfection with pre-miRNA589 partially reversed these EMT changes.Conclusion. miRNA589 mediates TGFβ1 induced EMT in human peritoneal mesothelial cells.

scholarly journals MiR-200a negatively regulates TGF-β1-induced epithelial-mesenchymal transition of peritoneal mesothelial cells by targeting ZEB1/2 expression

2018 ◽  
Vol 314 (6) ◽  
pp. F1087-F1095 ◽  
Author(s):  
Runsheng Guo ◽  
Guojun Hao ◽  
Yi Bao ◽  
Jun Xiao ◽  
Xiaojiang Zhan ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
De Novo ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Potential ◽  
Mesothelial Cells ◽  
Peritoneal Fibrosis ◽  
Close Link ◽  
Mesenchymal Transition ◽  
Peritoneal Mesothelial Cells ◽  
Collagen Expression

Although epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells was recognized as the key process of peritoneal fibrosis, which is a major cause of peritoneal failure related to peritoneal dialysis (PD), mechanisms underlying these processes remain largely unknown. In this study, we found that miR-200a was significantly downregulated in peritoneal tissues with fibrosis in a rat model of PD. In vitro, transforming growth factor (TGF)-β1-induced EMT, identified by de novo expression of α-smooth muscle actin and a loss of E-cadherin in human peritoneal mesothelial cells (HPMCs), was associated with downregulation of miR-200a but upregulation of zinc finger E-box-binding homeobox 1/2 (ZEB1/2), suggesting a close link between miR-200a and ZEB1/2 in TGF-β1-induced EMT. It was further demonstrated that miR-200a was able to bind to the 3′UTR of ZEB1/2, and overexpression of miR-200a blocked TGF-β1-induced upregulation of ZEB1/2 and, therefore, inhibited EMT and collagen expression. In contrast, overexpression ZEB1/2 blocked miR-200a inhibition of EMT and collagen expression in HMPCs. In conclusion, miR-200a could negatively regulate TGF-β1-induced EMT by targeting ZEB1/2 in peritoneal mesothelial cells. Blockade of EMT in HPMCS indicates the therapeutic potential of miR-200a as a treatment for peritoneal fibrosis associated with PD.

Lithium preserves peritoneal membrane integrity by suppressing mesothelial cell αB-crystallin

2021 ◽  
Vol 13 (608) ◽  
pp. eaaz9705
Author(s):  
Rebecca Herzog ◽  
Juan Manuel Sacnun ◽  
Guadalupe González-Mateo ◽  
Maria Bartosova ◽  
Katarzyna Bialas ◽  
...  
Keyword(s):  
Cell Injury ◽  
Membrane Integrity ◽  
Mesothelial Cell ◽  
Mesothelial Cells ◽  
Cell Protein ◽  
Dependent Manner ◽  
Peritoneal Membrane ◽  
Peritoneal Fibrosis ◽  
Mesenchymal Transition ◽  
Αb Crystallin

Life-saving renal replacement therapy by peritoneal dialysis (PD) is limited in use and duration by progressive impairment of peritoneal membrane integrity and homeostasis. Preservation of peritoneal membrane integrity during chronic PD remains an urgent but long unmet medical need. PD therapy failure results from peritoneal fibrosis and angiogenesis caused by hypertonic PD fluid (PDF)–induced mesothelial cytotoxicity. However, the pathophysiological mechanisms involved are incompletely understood, limiting identification of therapeutic targets. We report that addition of lithium chloride (LiCl) to PDF is a translatable intervention to counteract PDF-induced mesothelial cell death, peritoneal membrane fibrosis, and angiogenesis. LiCl improved mesothelial cell survival in a dose-dependent manner. Combined transcriptomic and proteomic characterization of icodextrin-based PDF-induced mesothelial cell injury identified αB-crystallin as the mesothelial cell protein most consistently counter-regulated by LiCl. In vitro and in vivo overexpression of αB-crystallin triggered a fibrotic phenotype and PDF-like up-regulation of vascular endothelial growth factor (VEGF), CD31-positive cells, and TGF-β–independent activation of TGF-β–regulated targets. In contrast, αB-crystallin knockdown decreased VEGF expression and early mesothelial-to-mesenchymal transition. LiCl reduced VEGF release and counteracted fibrosis- and angiogenesis-associated processes. αB-crystallin in patient-derived mesothelial cells was specifically up-regulated in response to PDF and increased in peritoneal mesothelial cells from biopsies from pediatric patients undergoing PD, correlating with markers of angiogenesis and fibrosis. LiCl-supplemented PDF promoted morphological preservation of mesothelial cells and the submesothelial zone in a mouse model of chronic PD. Thus, repurposing LiCl as a cytoprotective PDF additive may offer a translatable therapeutic strategy to combat peritoneal membrane deterioration during PD therapy.

The John F. Maher Recipient Lecture 2004: Rage in the Peritoneum

2005 ◽  
Vol 25 (1) ◽  
pp. 8-11 ◽  
Author(s):  
An S. De Vriese
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
High Glucose ◽  
Transforming Growth Factor ◽  
Degradation Products ◽  
Mesothelial Cells ◽  
Cell Surface Receptor ◽  
Peritoneal Membrane ◽  
Peritoneal Fibrosis ◽  
Mesenchymal Transition

Several conditions in the peritoneal membrane of peritoneal dialysis (PD) patients promote the accumulation of advanced glycation end-products (AGEs), that is, the uremic state, exposure to high glucose concentrations, and exposure to glucose degradation products (GDPs). AGEs exert some of their biologic actions through binding with a cell surface receptor, termed RAGE. Interaction of AGEs with RAGE induces sustained cellular activation, including the production of the fibrogenic growth factor, transforming growth factor-beta (TGF-β). TGF-β is pivotal in the process of epithelial-to-mesenchymal transition, through which cells of epithelial origin acquire myofibroblastic characteristics. Myofibroblasts are involved in virtually all conditions of pathological fibrosis. Submesothelial fibrosis is an important feature in peritoneal biopsies of PD patients, especially of those with clinical problems. We therefore examined the role of RAGE in peritoneal fibrosis, in an animal model of uremia, of high glucose exposure, and of peritoneal dialysate exposure. All three models were characterized by accumulation of AGEs, upregulation of RAGE, and fibrosis. Antagonism of RAGE prevented the upregulation of TGF-β and fibrosis in the peritoneal membrane. We further examined the underlying mechanism of peritoneal fibrosis in the uremic model. Prominent myofibroblast transdifferentiation of mesothelial cells was identified by co-localization of cytokeratin and α-smooth muscle actin in submesothelial and interstitial fibrotic tissue. Antagonism of RAGE prevented conversion of mesothelial cells to myofibroblasts in uremia. In conclusion, we hypothesize that accumulation of AGEs in the peritoneal membrane, as a consequence of the uremic environment, chronic exposure to high glucose, and exposure to GDPs, results in an increased expression of RAGE. The interaction of AGEs with RAGE induces peritoneal fibrosis by virtue of upregulation of TGF-β and subsequent conversion of mesothelial cells into myofibroblasts.

scholarly journals HIF-1α mediates Hypoxia-induced epithelial–mesenchymal transition in peritoneal mesothelial cells

Renal Failure ◽  
2015 ◽  
Vol 38 (2) ◽  
pp. 282-289 ◽  
Author(s):  
Yoshiyuki Morishita ◽  
Susumu Ookawara ◽  
Ichiro Hirahara ◽  
Shigeaki Muto ◽  
Daisuke Nagata
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Mesothelial Cells ◽  
Mesenchymal Transition ◽  
Peritoneal Mesothelial Cells
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