Fluvastatin inhibits the expression of fibronectin in human peritoneal mesothelial cells induced by high-glucose peritoneal dialysis solution via SGK1 pathway

Zhang, Li; Liu, Jia; Xu, Yang; Zhao, Xianxian; Qian, Jun; Sun, Bin; Xing, Changying

doi:10.1007/s10157-014-0991-0

Cited by 5 publications

(6 citation statements)

References 25 publications

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“…Other cell sources that may be used for mesothelial repair include bone marrow derived cells ( Sekiguchi et al, 2012 ), adipose-derived stem cells ( Kim et al, 2014 ), and mesenchymal stem cells ( Wang et al, 2012 ; Ueno et al, 2013 ). Alternative therapeutic strategies being investigated to reduce mesothelial cell-mediated inflammation and prevent peritoneal fibrosis include targeting TGFβ1-mediated mechanisms ( Hung et al, 2001 , 2003 ; Yung et al, 2001 ; Margetts et al, 2002a ; Fang et al, 2006 ; Tomino, 2012 ; Jang et al, 2013 ), reducing mesothelial cell production of fibronectin ( Tong et al, 2012 ; Zhang et al, 2014 ) developing a more bio compatible PD solution ( Bajo et al, 2000 ; Le Poole et al, 2005 ), altering PD daily dwelling time ( Lee et al, 2014 ), and stimulating fibrinolytic agents ( Haslinger et al, 2003 ).…”

Section: The Mesothelial Cell In Fibrotic Disordersmentioning

confidence: 99%

Mesothelial cells in tissue repair and fibrosis

et al. 2015

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Mesothelial cells are fundamental to the maintenance of serosal integrity and homeostasis and play a critical role in normal serosal repair following injury. However, when normal repair mechanisms breakdown, mesothelial cells take on a profibrotic role, secreting inflammatory, and profibrotic mediators, differentiating and migrating into the injured tissues where they contribute to fibrogenesis. The development of new molecular and cell tracking techniques has made it possible to examine the origin of fibrotic cells within damaged tissues and to elucidate the roles they play in inflammation and fibrosis. In addition to secreting proinflammatory mediators and contributing to both coagulation and fibrinolysis, mesothelial cells undergo mesothelial-to-mesenchymal transition, a process analogous to epithelial-to-mesenchymal transition, and become fibrogenic cells. Fibrogenic mesothelial cells have now been identified in tissues where they have not previously been thought to occur, such as within the parenchyma of the fibrotic lung. These findings show a direct role for mesothelial cells in fibrogenesis and open therapeutic strategies to prevent or reverse the fibrotic process.

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Section: The Mesothelial Cell In Fibrotic Disordersmentioning

confidence: 99%

Mesothelial cells in tissue repair and fibrosis

et al. 2015

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“…Melatonin can reverse lipopolysaccharide-induced EMT (54). Fluvastatin inhibits high glucose-based PD-induced fibronectin expression in human PMCs via the serum-and glucocorticoid-inducible kinase 1 pathway (55). The histone acetyltransferase inhibitor C646 reverses EMT in human PMCs via the TGF-β/Smad3 signaling pathway (56).…”

Section: Discussionmentioning

confidence: 99%

Effect of astragaloside IV and the role of nuclear receptor RXRα in human peritoneal mesothelial cells in high glucose‑based peritoneal dialysis fluids

et al. 2019

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Peritoneal fibrosis is a serious complication that can occur during peritoneal dialysis (PD), which is primarily caused by damage to peritoneal mesothelial cells (PMCs). The onset of peritoneal fibrosis is delayed or inhibited by promoting PMC survival and inhibiting PMC epithelial-to-mesenchymal transition (EMT). In the present study, the effect of astragaloside IV and the role of the nuclear receptor retinoid X receptor-α (RXRα) in PMCs in high glucose-based PD fluids was investigated. Human PMC HMrSV5 cells were transfected with RXRα short hairpin RNA (shRNA), or an empty vector, and then treated with PD fluids and astragaloside IV. Cell viability, apoptosis and EMT were examined using the Cell Counting Kit-8 assay and flow cytometry, and by determining the levels of caspase-3, E-cadherin and α-smooth muscle actin (α-SMA) via western blot analysis. Cell viability and apoptosis were increased, as were the levels of E-cadherin in HMrSV5 cells following treatment with PD fluid. The protein levels of α-SMA and caspase-3 were increased by treatment with PD fluid. Exposure to astragaloside IV inhibited these changes; however, astragaloside IV did not change cell viability, apoptosis, E-cadherin or α-SMA levels in HMrSV5 cells under normal conditions. Transfection of HMrSV5 cells with RXRα shRNA resulted in decreased viability and E-cadherin expression, and increased apoptosis and α-SMA levels, in HMrSV5 cells treated with PD fluids and co-treated with astragaloside IV or vehicle. These results suggested that astragaloside IV increased cell viability, and inhibited apoptosis and EMT in PMCs in PD fluids, but did not affect these properties of PMCs under normal condition. Thus, the present study suggested that RXRα is involved in maintaining viability, inhibiting apoptosis and reducing EMT of PMCs in PD fluid.

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“…Numbers of sequences per sample are summarized in Table S1 . Next, sequences were mapped against human genome (release GRCh38.p10) using TopHat [ 85 , 86 ] and reads were annotated using the corresponding Hs38-gtf file. The whole bioinformatic protocol was executed using the RNAseq pipeline app of the GPRO-suite [ 87 ].…”

Section: Methodsmentioning

confidence: 99%

“…Eight samples showed significantly low mapping yields and were removed from the study ( Table S1 ). Thus, a final number of 11 samples (7 PHV and 4 no PHV) averaging 16 million reads were used for differential expression analysis, made using Cufflinks/CuffDiff [ 85 , 86 ] to compare the expression of PHV vs. no PHV. We filtered out those entries whose detection levels were lower than 40 reads (sum of averages from PHV and no PHV groups) and finally found a number of 1666 molecules which were considered as positively detected.…”

Section: Methodsmentioning

confidence: 99%

Increased miR-7641 Levels in Peritoneal Hyalinizing Vasculopathy in Long-Term Peritoneal Dialysis Patients

Díaz

Sandoval

Rodrigues-Díez

et al. 2020

IJMS

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Peritoneal hyalinizing vasculopathy (PHV) represents the cornerstone of long-term peritoneal dialysis (PD), and especially characterizes patients associated with encapsulating peritoneal sclerosis. However, the mechanisms of PHV development remain unknown. A cross sectional study was performed in 100 non-selected peritoneal biopsies of PD patients. Clinical data were collected and lesions were evaluated by immunohistochemistry. In selected biopsies a microRNA (miRNA)-sequencing analysis was performed. Only fifteen patients (15%) showed PHV at different degrees. PHV prevalence was significantly lower among patients using PD fluids containing low glucose degradation products (GDP) (5.9% vs. 24.5%), angiotensin converting enzyme inhibitors (ACEIs) (7.5% vs. 23.4%), statins (6.5% vs. 22.6%) or presenting residual renal function, suggesting the existence of several PHV protective factors. Peritoneal biopsies from PHV samples showed loss of endothelial markers and induction of mesenchymal proteins, associated with collagen IV accumulation and wide reduplication of the basement membrane. Moreover, co-expression of endothelial and mesenchymal markers, as well as TGF-β1/Smad3 signaling activation were found in PHV biopsies. These findings suggest that an endothelial-to-mesenchymal transition (EndMT) process was taking place. Additionally, significantly higher levels of miR-7641 were observed in severe PHV compared to non-PHV peritoneal biopsies. Peritoneal damage by GDPs induce miRNA deregulation and an EndMT process in submesothelial vessels, which could contribute to collagen IV accumulation and PHV.

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Fluvastatin inhibits the expression of fibronectin in human peritoneal mesothelial cells induced by high-glucose peritoneal dialysis solution via SGK1 pathway

Cited by 5 publications

References 25 publications

Mesothelial cells in tissue repair and fibrosis

Mesothelial cells in tissue repair and fibrosis

Effect of astragaloside IV and the role of nuclear receptor RXRα in human peritoneal mesothelial cells in high glucose‑based peritoneal dialysis fluids

Increased miR-7641 Levels in Peritoneal Hyalinizing Vasculopathy in Long-Term Peritoneal Dialysis Patients

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