scholarly journals Histone deacetylase 6 inhibition counteracts the epithelial-mesenchymal transition of peritoneal mesothelial cells and prevents peritoneal fibrosis

Oncotarget ◽  
2017 ◽  
Vol 8 (51) ◽  
pp. 88730-88750 ◽  
Author(s):  
Liuqing Xu ◽  
Na Liu ◽  
Hongwei Gu ◽  
Hongrui Wang ◽  
Yingfeng Shi ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Epithelial Mesenchymal Transition ◽  
Mesothelial Cells ◽  
Histone Deacetylase 6 ◽  
Peritoneal Fibrosis ◽  
Mesenchymal Transition ◽  
Peritoneal Mesothelial Cells

scholarly journals Requirement of Histone Deacetylase 6 for Interleukin-6 Induced Epithelial-Mesenchymal Transition, Proliferation, and Migration of Peritoneal Mesothelial Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Yingfeng Shi ◽  
Min Tao ◽  
Jun Ni ◽  
Lunxian Tang ◽  
Feng Liu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Histone Deacetylase ◽  
Epithelial Mesenchymal Transition ◽  
Histone Deacetylase 6 ◽  
Peritoneal Fibrosis ◽  
Mesenchymal Transition ◽  
Peritoneal Mesothelial Cells ◽  
And Migration ◽  
Proliferation And Migration

Aims: Influenced by microenvironment, human peritoneal mesothelial cells (HPMCs) acquired fibrotic phenotype, which was identified as the protagonist for peritoneal fibrosis. In this study, we examined the role of histone deacetylase 6 (HDAC6) for interleukin-6 (IL-6) induced epithelial-mesenchymal transition (EMT), proliferation, and migration of HPMCs.Methods: The role of HDAC6 in IL-6-elicited EMT of HPMCs was tested by morphological observation of light microscope, immunoblotting, and immune-fluorescence assay; and the function of HDAC6 in proliferation and migration of HPMCs was examined by CCK-8 assay, wound healing experiment, and immunoblotting.Results: IL-6 stimulation significantly increased the expression of HDAC6. Treatment with tubastatin A (TA), a highly selective HDAC6 inhibitor, or silencing of HDAC6 with siRNA decreased the expression of HDAC6. Moreover, TA or HDAC6 siRNA suppressed IL-6-induced EMT, as evidenced by decreased expressions of α-SMA, Fibronectin, and collagen I and the preserved expression of E-cadherin in cultured HPMCs. Mechanistically, HDAC6 inhibition suppressed the expression of transforming growth factor β (TGFβ) receptor I (TGFβRI), phosphorylation of Smad3, secretion of connective tissue growth factor (CTGF), and transcription factor Snail. On the other hand, the pharmacological inhibition or genetic target of HDAC6 suppressed HPMCs proliferation, as evidenced by the decreased optical density of CCK-8 and the expressions of PCNA and Cyclin E. The migratory rate of HPMCs also decreased. Mechanistically, HDAC6 inhibition blocked the activation of JAK2 and STAT3.Conclusion: Our study illustrated that IL-6-induced HDAC6 not only regulated IL-6 itself downstream JAK2/STAT3 signaling but also co-activated the TGF-β/Smad3 signaling, leading to the change of the phenotype and mobility of HPMCs. HDAC6 could be a potential therapeutic target for the prevention and treatment of peritoneal fibrosis.

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.

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

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
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