scholarly journals Non-Coding RNAs as New Therapeutic Targets in the Context of Renal Fibrosis

2019 ◽  
Vol 20 (8) ◽  
pp. 1977 ◽  
Author(s):  
Cynthia Van der Hauwaert ◽  
François Glowacki ◽  
Nicolas Pottier ◽  
Christelle Cauffiez
Keyword(s):  
Renal Fibrosis ◽  
Molecular Mechanisms ◽  
Tissue Injury ◽  
Kidney Diseases ◽  
Therapeutic Targets ◽  
Future Research ◽  
Kidney Fibrosis ◽  
Extracellular Matrix Components ◽  
Non Coding Rnas ◽  
New Therapeutic Targets

Fibrosis, or tissue scarring, is defined as the excessive, persistent and destructive accumulation of extracellular matrix components in response to chronic tissue injury. Renal fibrosis represents the final stage of most chronic kidney diseases and contributes to the progressive and irreversible decline in kidney function. Limited therapeutic options are available and the molecular mechanisms governing the renal fibrosis process are complex and remain poorly understood. Recently, the role of non-coding RNAs, and in particular microRNAs (miRNAs), has been described in kidney fibrosis. Seminal studies have highlighted their potential importance as new therapeutic targets and innovative diagnostic and/or prognostic biomarkers. This review will summarize recent scientific advances and will discuss potential clinical applications as well as future research directions.

scholarly journals Emerging Roles of Long Non-Coding RNAs in Renal Fibrosis

Life ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 131
Author(s):  
Jinwen Lin ◽  
Zhengqian Jiang ◽  
Chenxi Liu ◽  
Dawei Zhou ◽  
Jiayu Song ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Cell Function ◽  
Therapeutic Targets ◽  
Current Evidence ◽  
Kidney Fibrosis ◽  
Rna Molecules ◽  
Renal Replacement Therapies ◽  
Non Coding Rnas ◽  
Nuclear Domains ◽  
End Stage

Renal fibrosis is an unavoidable consequence that occurs in nearly all of the nephropathies. It is characterized by a superabundant deposition and accumulation of extracellular matrix (ECM). All compartments in the kidney can be affected, including interstitium, glomeruli, vasculature, and other connective tissue, during the pathogenesis of renal fibrosis. The development of this process eventually causes destruction of renal parenchyma and end-stage renal failure, which is a devastating disease that requires renal replacement therapies. Recently, long non-coding RNAs (lncRNAs) have been emerging as key regulators governing gene expression and affecting various biological processes. These versatile roles include transcriptional regulation, organization of nuclear domains, and the regulation of RNA molecules or proteins. Current evidence proposes the involvement of lncRNAs in the pathologic process of kidney fibrosis. In this review, the biological relevance of lncRNAs in renal fibrosis will be clarified as important novel regulators and potential therapeutic targets. The biology, and subsequently the current understanding, of lncRNAs in renal fibrosis are demonstrated—highlighting the involvement of lncRNAs in kidney cell function, phenotype transition, and vascular damage and rarefaction. Finally, we discuss challenges and future prospects of lncRNAs in diagnostic markers and potential therapeutic targets, hoping to further inspire the management of renal fibrosis.

scholarly journals Long Non-coding RNA: An Emerging Contributor and Potential Therapeutic Target in Renal Fibrosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Weiping Xia ◽  
Yao He ◽  
Yu Gan ◽  
Bo Zhang ◽  
Guoyu Dai ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Molecular Mechanisms ◽  
Pathological Process ◽  
Major Type ◽  
Future Research ◽  
Non Coding Rna ◽  
Future Research Directions ◽  
Non Coding Rnas ◽  
Long Non Coding Rna

Renal fibrosis (RF) is a pathological process that culminates in terminal renal failure in chronic kidney disease (CKD). Fibrosis contributes to progressive and irreversible decline in renal function. However, the molecular mechanisms involved in RF are complex and remain poorly understood. Long non-coding RNAs (lncRNAs) are a major type of non-coding RNAs, which significantly affect various disease processes, cellular homeostasis, and development through multiple mechanisms. Recent investigations have implicated aberrantly expressed lncRNA in RF development and progression, suggesting that lncRNAs play a crucial role in determining the clinical manifestation of RF. In this review, we comprehensively evaluated the recently published articles on lncRNAs in RF, discussed the potential application of lncRNAs as diagnostic and/or prognostic biomarkers, proposed therapeutic targets for treating RF-associated diseases and subsequent CKD transition, and highlight future research directions in the context of the role of lncRNAs in the development and treatment of RF.

Fate alteration of bone marrow-derived macrophages ameliorates kidney fibrosis in murine model of unilateral ureteral obstruction

2018 ◽  
Vol 34 (10) ◽  
pp. 1657-1668 ◽  
Author(s):  
Ying Yang ◽  
Xiaojian Feng ◽  
Xinyan Liu ◽  
Ying Wang ◽  
Min Hu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Kidney Diseases ◽  
Unilateral Ureteral Obstruction ◽  
Immunofluorescent Staining ◽  
Enzyme Linked Immunosorbent Assay ◽  
Pathological Feature ◽  
Kidney Fibrosis ◽  
Anti Inflammatory

AbstractBackgroundRenal fibrosis is a key pathological feature and final common pathway leading to end-stage kidney failure in many chronic kidney diseases. Myofibroblast is the master player in renal fibrosis. However, myofibroblasts are heterogeneous. Recent studies show that bone marrow-derived macrophages transform into myofibroblasts by transforming growth factor (TGF)-β-induced macrophage–myofibroblast transition (MMT) in renal fibrosis.MethodsTGF-β signaling was redirected by inhibition of β-catenin/T-cell factor (TCF) to increase β-catenin/Foxo in bone marrow-derived macrophages. A kidney fibrosis model of unilateral ureteral obstruction was performed in EGFP bone marrow chimera mouse. MMT was examined by flow cytometry analysis of GFP+F4/80+α-SMA+ cells from unilateral ureteral obstruction (UUO) kidney, and by immunofluorescent staining of bone marrow-derived macrophages in vitro. Inflammatory and anti-inflammatory cytokines were analysis by enzyme-linked immunosorbent assay.ResultsInhibition of β-catenin/TCF by ICG-001 combined with TGF-β1 treatment increased β-catenin/Foxo1, reduced the MMT and inflammatory cytokine production by bone marrow-derived macrophages, and thereby, reduced kidney fibrosis in the UUO model.ConclusionsOur results demonstrate that diversion of β-catenin from TCF to Foxo1-mediated transcription not only inhibits the β-catenin/TCF-mediated fibrotic effect of TGF-β, but also enhances its anti-inflammatory action, allowing therapeutic use of TGF-β to reduce both inflammation and fibrosis at least partially by changing the fate of bone marrow-derived macrophages.

scholarly journals Bioinformatic Reconstruction and Analysis of Gene Networks Related to Glucose Variability in Diabetes and Its Complications

2020 ◽  
Vol 21 (22) ◽  
pp. 8691
Author(s):  
Olga V. Saik ◽  
Vadim V. Klimontov
Keyword(s):  
Gene Networks ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Enrichment Analysis ◽  
Glucose Variability ◽  
Future Research ◽  
Muscle Tissues ◽  
New Gene ◽  
Occupy Central ◽  
Glycogen Biosynthesis

Glucose variability (GV) has been recognized recently as a promoter of complications and therapeutic targets in diabetes. The aim of this study was to reconstruct and analyze gene networks related to GV in diabetes and its complications. For network analysis, we used the ANDSystem that provides automatic network reconstruction and analysis based on text mining. The network of GV consisted of 37 genes/proteins associated with both hyperglycemia and hypoglycemia. Cardiovascular system, pancreas, adipose and muscle tissues, gastrointestinal tract, and kidney were recognized as the loci with the highest expression of GV-related genes. According to Gene Ontology enrichment analysis, these genes are associated with insulin secretion, glucose metabolism, glycogen biosynthesis, gluconeogenesis, MAPK and JAK-STAT cascades, protein kinase B signaling, cell proliferation, nitric oxide biosynthesis, etc. GV-related genes were found to occupy central positions in the networks of diabetes complications (cardiovascular disease, diabetic nephropathy, retinopathy, and neuropathy) and were associated with response to hypoxia. Gene prioritization analysis identified new gene candidates (THBS1, FN1, HSP90AA1, EGFR, MAPK1, STAT3, TP53, EGF, GSK3B, and PTEN) potentially involved in GV. The results expand the understanding of the molecular mechanisms of the GV phenomenon in diabetes and provide molecular markers and therapeutic targets for future research.

scholarly journals Functional Screening Techniques to Identify Long Non-Coding RNAs as Therapeutic Targets in Cancer

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3695
Author(s):  
Kathleen M. Lucere ◽  
Megan M. R. O’Malley ◽  
Sarah D. Diermeier
Keyword(s):  
Antisense Oligonucleotides ◽  
High Throughput Screening ◽  
Large Scale ◽  
Therapeutic Targets ◽  
Functional Screening ◽  
Protein Coding ◽  
Non Coding Rnas ◽  
New Therapeutic Targets ◽  
Functional Screens ◽  
Screening Approaches

Recent technological advancements such as CRISPR/Cas-based systems enable multiplexed, high-throughput screening for new therapeutic targets in cancer. While numerous functional screens have been performed on protein-coding genes to date, long non-coding RNAs (lncRNAs) represent an emerging class of potential oncogenes and tumor suppressors, with only a handful of large-scale screens performed thus far. Here, we review in detail currently available screening approaches to identify new lncRNA drivers of tumorigenesis and tumor progression. We discuss the various approaches of genomic and transcriptional targeting using CRISPR/Cas9, as well as methods to post-transcriptionally target lncRNAs via RNA interference (RNAi), antisense oligonucleotides (ASOs) and CRISPR/Cas13. We discuss potential advantages, caveats and future applications of each method to provide an overview and guide on investigating lncRNAs as new therapeutic targets in cancer.

scholarly journals Extracellular Matrix in Kidney Fibrosis: More Than Just a Scaffold

2019 ◽  
Vol 67 (9) ◽  
pp. 643-661 ◽  
Author(s):  
Roman David Bülow ◽  
Peter Boor
Keyword(s):  
Extracellular Matrix ◽  
Renal Fibrosis ◽  
Kidney Diseases ◽  
Dynamic Structure ◽  
Renal Diseases ◽  
Chronic Kidney Diseases ◽  
Kidney Fibrosis ◽  
Non Invasive ◽  
Ecm Proteins ◽  
Diagnostic Approaches

Kidney fibrosis is the common histological end-point of progressive, chronic kidney diseases (CKDs) regardless of the underlying etiology. The hallmark of renal fibrosis, similar to all other organs, is pathological deposition of extracellular matrix (ECM). Renal ECM is a complex network of collagens, elastin, and several glycoproteins and proteoglycans forming basal membranes and interstitial space. Several ECM functions beyond providing a scaffold and organ stability are being increasingly recognized, for example, in inflammation. ECM composition is determined by the function of each of the histological compartments of the kidney, that is, glomeruli, tubulo-interstitium, and vessels. Renal ECM is a dynamic structure undergoing remodeling, particularly during fibrosis. From a clinical perspective, ECM proteins are directly involved in several rare renal diseases and indirectly in CKD progression during renal fibrosis. ECM proteins could serve as specific non-invasive biomarkers of fibrosis and scaffolds in regenerative medicine. The gold standard and currently only specific means to measure renal fibrosis is renal biopsy, but new diagnostic approaches are appearing. Here, we discuss the localization, function, and remodeling of major renal ECM components in healthy and diseased, fibrotic kidneys and the potential use of ECM in diagnostics of renal fibrosis and in tissue engineering.

Twist1 Regulates Macrophage Plasticity To Promote Renal Fibrosis Through Galectin-3

2021 ◽  
Author(s):  
Qingfeng Wu ◽  
Shiren Sun ◽  
Lei Wei ◽  
Minna Liu ◽  
Hao Liu ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Molecular Mechanisms ◽  
Interstitial Fibrosis ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
Kidney Fibrosis ◽  
Galectin 3 ◽  
M2 Macrophage Polarization ◽  
Macrophage Plasticity ◽  
Stage Renal Disease

Abstract Renal interstitial fibrosis is the pathological basis of end-stage renal disease, in which the heterogeneity of macrophages in renal microenvironment plays an important role. However, the molecular mechanisms of macrophage plasticity during renal fibrosis progression remain unclear. In this study, we found for the first time that increased expression of Twist1 in macrophages was significantly associated with the severity of renal fibrosis in IgA nephropathy patients and mice with unilateral ureteral obstruction (UUO). Ablation of Twist1 in macrophages markedly alleviated renal tubular injury and renal fibrosis in UUO mice, accompanied by a lower extent of macrophage infiltration and M2 polarization in the kidney. The knockdown of Twist1 inhibited the chemotaxis and migration of macrophages, at least partially, through the CCL2/CCR2 axis. Twist1 downregulation inhibited M2 macrophage polarization and reduced the secretion of the profibrotic factors Arg1, MR (CD206), IL-10, and TGF-β. Galectin-3 was decreased in the macrophages of the conditional Twist1-deficient mice, and Twist1 was shown to directly activate galectin-3 transcription. Up-regulation of galectin-3 recovered Twist1-mediated M2 macrophage polarization. In conclusion, Twist1/galectin-3 signaling regulates macrophage plasticity (M2 phenotype) and promotes renal fibrosis. This study could suggest new strategies for delaying kidney fibrosis in patients with chronic kidney disease.

scholarly journals Autophagy in Alcohol-Induced Multiorgan Injury: Mechanisms and Potential Therapeutic Targets

2014 ◽  
Vol 2014 ◽  
pp. 1-20 ◽  
Author(s):  
Yuan Li ◽  
Shaogui Wang ◽  
Hong-Min Ni ◽  
Heqing Huang ◽  
Wen-Xing Ding
Keyword(s):  
Molecular Mechanisms ◽  
Tissue Injury ◽  
Current Knowledge ◽  
Therapeutic Targets ◽  
Degradation Pathway ◽  
Protective Mechanism ◽  
Intracellular Degradation ◽  
Injury Mechanisms ◽  
Evolutionarily Conserved

Autophagy is a genetically programmed, evolutionarily conserved intracellular degradation pathway involved in the trafficking of long-lived proteins and cellular organelles to the lysosome for degradation to maintain cellular homeostasis. Alcohol consumption leads to injury in various tissues and organs including liver, pancreas, heart, brain, and muscle. Emerging evidence suggests that autophagy is involved in alcohol-induced tissue injury. Autophagy serves as a cellular protective mechanism against alcohol-induced tissue injury in most tissues but could be detrimental in heart and muscle. This review summarizes current knowledge about the role of autophagy in alcohol-induced injury in different tissues/organs and its potential molecular mechanisms as well as possible therapeutic targets based on modulation of autophagy.

Sign in / Sign up

Export Citation Format

Share Document