Noncoding RNAs in peritoneal fibrosis: Background, Mechanism, and Therapeutic Approach

Guo, Yanhong; Wang, Liuwei; Gou, Rong; Tang, Lin; Li, Peipei

doi:10.1016/j.biopha.2020.110385

Cited by 14 publications

(13 citation statements)

References 141 publications

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“…Several miRNAs have been described so far to impact peritoneal fibrosis [24,25]. In particular, some miRNAs were characterized for their inhibitory effect on fibrosis: miR-15 was described to suppress inflammation and fibrosis of MCs through VEGF inhibition [26]; miR-30a negatively regulated TGF-β1-induced EMT and peritoneal fibrosis by targeting Snai1 [27]; miR-9-5p suppressed pro-fibrogenic transformation of fibroblasts and MCs from PD patients [28]; miR-302c modulated peritoneal dialysisassociated fibrosis by targeting CTGF [29]; miR-29b inhibited peritoneal fibrosis in a mouse model of PD [30].…”

Section: Discussionmentioning

confidence: 99%

Restoration of WT1/miR-769-5p axis by HDAC1 inhibition promotes MMT reversal in mesenchymal-like mesothelial cells

et al. 2022

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Histone acetylation/deacetylation play an essential role in modifying chromatin structure and in regulating cell plasticity in eukaryotic cells. Therefore, histone deacetylase (HDAC) pharmacological inhibitors are promising tools in the therapy of fibrotic diseases and in cancer. Peritoneal fibrosis is a pathological process characterized by many cellular and molecular alterations, including the acquisition of invasive/pro-fibrotic abilities by mesothelial cells (MCs) through induction of mesothelial to mesenchymal transition (MMT). The aim of this study was to characterize the molecular mechanism of the antifibrotic role of HDAC1 inhibition. Specifically, treatment with MS-275, an HDAC1-3 inhibitor previously known to promote MMT reversal, induced the expression of several TGFBRI mRNA-targeting miRNAs. Among them, miR-769-5p ectopic expression was sufficient to promote MMT reversal and to limit MC migration and invasion, whereas miR-769-5p silencing further enhanced mesenchymal gene expression. These results were confirmed by HDAC1 genetic silencing. Interestingly, miR-769-5p silencing maintained mesenchymal features despite HDAC1 inhibition, thus indicating that it is necessary to drive MMT reversal induced by HDAC1 inhibition. Besides TGFBRI, miR-769-5p was demonstrated to target SMAD2/3 and PAI-1 expression directly. When analyzing molecular mechanisms underlying miR-769-5p expression, we found that the transcription factor Wilms’ tumor 1 (WT1), a master gene controlling MC development, binds to the miR-769-5p promoter favoring its expression. Interestingly, both WT1 expression and binding to miR-769-5p promoter were increased by HDAC1 inhibition and attenuated by TGFβ1 treatment. Finally, we explored the significance of these observations in the cell-to-cell communication: we evaluated the ability of miR-769-5p to be loaded into extracellular vesicles (EVs) and to promote MMT reversal in recipient mesenchymal-like MCs. Treatment of fibrotic MCs with EVs isolated from miR-769-5p over-expressing MCs promoted the down-regulation of specific mesenchymal targets and the reacquisition of an epithelial-like morphology. In conclusion, we highlighted an HDAC1-WT1-miR-769-5p axis potentially relevant for therapies aimed at counteracting organ fibrosis.

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Section: Discussionmentioning

confidence: 99%

Restoration of WT1/miR-769-5p axis by HDAC1 inhibition promotes MMT reversal in mesenchymal-like mesothelial cells

et al. 2022

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“…Micro RNAs (miRNAs) are the most studied non-coding RNAs. Different miRNAs have been found in PD effluents and have been associated with peritoneal function and damage parameters [ 215 ]. Most of them have been studied in vitro , whereas few studies have been performed on in vivo models.…”

Section: Potential Anti-inflammatory Treatments In the Preservation O...mentioning

confidence: 99%

Novel Aspects of the Immune Response Involved in the Peritoneal Damage in Chronic Kidney Disease Patients under Dialysis

Trionfetti

Marchant

González-Mateo

et al. 2023

IJMS

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Chronic kidney disease (CKD) incidence is growing worldwide, with a significant percentage of CKD patients reaching end-stage renal disease (ESRD) and requiring kidney replacement therapies (KRT). Peritoneal dialysis (PD) is a convenient KRT presenting benefices as home therapy. In PD patients, the peritoneum is chronically exposed to PD fluids containing supraphysiologic concentrations of glucose or other osmotic agents, leading to the activation of cellular and molecular processes of damage, including inflammation and fibrosis. Importantly, peritonitis episodes enhance peritoneum inflammation status and accelerate peritoneal injury. Here, we review the role of immune cells in the damage of the peritoneal membrane (PM) by repeated exposure to PD fluids during KRT as well as by bacterial or viral infections. We also discuss the anti-inflammatory properties of current clinical treatments of CKD patients in KRT and their potential effect on preserving PM integrity. Finally, given the current importance of coronavirus disease 2019 (COVID-19) disease, we also analyze here the implications of this disease in CKD and KRT.

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“…ncRNA'ların temel işlevi, transkripsiyonel, posttranskripsiyonel ve post-translasyonel süreçleri regüle ederek gen ekspresyonunu düzenlemektir. 24 ncRNA'lar kromatin mimarisi, epigenetik modifikasyonların düzenlenmesi ve genom stabilitesinin korunması gibi süreçlerde yapı iskelesi görevi görür. 25 Birçok ncRNA türü karakterize edilip, fonksiyonel olarak referans (housekeeping) ve regülatör olmak üzere iki ana gruba ayrılmıştır.…”

Section: Koronavirüslerin Yapısı Ve Replikasyonuunclassified

“…Argonaute (AGO) protein ailesi, miRNA dupleksinin oluşum sürecine aracılık etmektedir. 24 miRNA dupleksi, RISC'i mRNA'ya hedeflemekte ve translasyonun inhibisyonuna neden olmaktadır. 33 miRNA'lar hedef mRNA'nın 3'-UTR'sine bağlanarak, translasyonun stabilitesini inhibe etmektedir.…”

Section: Koronavirüslerin Yapısı Ve Replikasyonuunclassified

The Role of ncRNAs in Covid-19 Pathogenesis

Oz¹,

Pehlivan²,

Pirim³

2021

FORBES

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Genomic studies have shown that approximately 2% of the human genome encodes protein, and the rest consists of non-coding RNAs (ncRNA). ncRNAs are the modifications that can alter gene expression at different levels without making any changes on the DNA sequence. One of the most important function of non-coding RNAs is to modulate host immunity and inflammatory response by regulating chromatin structure and gene expression. The World Health Organization has declared Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) as Coronavirus Disease 2019 (COVID-19). COVID-19 shows symptoms such as fever, cough, shortness of breath and it can lead to severe symptomatic acute respiratory distress syndrome (ARDS), bring along many problems such as cardiovascular complications, kidney damage, stroke and death. Virus host interactions associated with the immune system is also important beside the viral replication mechanism in the development of a successful therapeutic target for SARS-CoV-2. Epigenetic mechanisms that regulate virus-host interactions affect the extent and adequacy of immune and inflammatory responses that are important for clinical outcomes. Thus, identifying ncRNAs involved in SARS-CoV-2 infection will help to understand the epigenetic regulation underlying the immune response that occurs and to develop new specific strategies to prevent and treat the infection. In this review, the importance of ncRNA mediated gene regulation in SARS-CoV-2 infection and its role in the ongoing COVID-19 pandemic were discussed.

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Noncoding RNAs in peritoneal fibrosis: Background, Mechanism, and Therapeutic Approach

Cited by 14 publications

References 141 publications

Restoration of WT1/miR-769-5p axis by HDAC1 inhibition promotes MMT reversal in mesenchymal-like mesothelial cells

Restoration of WT1/miR-769-5p axis by HDAC1 inhibition promotes MMT reversal in mesenchymal-like mesothelial cells

Novel Aspects of the Immune Response Involved in the Peritoneal Damage in Chronic Kidney Disease Patients under Dialysis

The Role of ncRNAs in Covid-19 Pathogenesis

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