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Fibrosis-Related lncRNA

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 March 2020) | Viewed by 31735

Special Issue Editors

Catholic University of Daegu, Daegu, Korea
Interests: lncRNA; fibrosis; inflammation; biologic marker; therapeutic target
Department of Biohealth Informatics, School of Informatics and Computing, Indiana University Purdue University Indianapolis (IUPUI), 535 West Michigan Street, Indianapolis, IN 46202, USA
Interests: transcriptomics; post-transcriptional regulation; RNA-binding proteins; epitranscriptomics; gene regulatory networks; systems biology; single molecule sequencing; RNA structure and interactions

Special Issue Information

Dear Colleagues, 

It is known that less than 2% of the transcribed genome encodes protein-coding RNA. Most noncoding transcripts are composed of more than 200 base pairs and constitute a group of long noncoding RNA (lncRNA). Many studies have shown that lncRNAs play key roles in a variety of biological processes, such as proliferation and apoptosis, through complex mechanisms. Recently, lncRNA has become a potential hot topic in diagnosing human disease and as biological markers in predicting the prognosis and treatment in cancer. They also play an important role in the development of fibrosis-related diseases in various organs including the liver, heart, lung, and kidney. Fibrosis is the excess deposition of extracellular matrix components, which can occur in multiple organs, and ultimately leads to organ failure. Although lncRNAs are important players in the initiation and progression of many pathological processes, the role of lncRNAs in organ fibrosis still remains largely undefined. LncRNA is also highly disease- and tissue-specific, and they could be an ideal therapeutic target for developing treatment against fibrosis-related disease.

This open-access Special Issue will bring together original research and review articles on the functions of lncRNAs in various fibrotic diseases of the liver, heart, kidney, lung, and peritoneum. Furthermore, this Special Issue systematically highlights the roles of lncRNAs and technical developments on the use of lncRNAs as diagnostic markers and therapeutic targets for their clinical use in human fibrotic diseases.

Dr. Kwan-Kyu Park
Dr. Sarath Chandra Janga
Guest Editors

Manuscript Submission Information

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Keywords

  • lncRNA
  • fibrosis
  • inflammation
  • biologic marker
  • therapeutic target

Published Papers (6 papers)

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Research

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14 pages, 2423 KiB  
Article
Anti-Fibrotic Effect of Synthetic Noncoding Decoy ODNs for TFEB in an Animal Model of Chronic Kidney Disease
by Sun-Jae Lee, Young-Ah Kim and Kwan-Kyu Park
Int. J. Mol. Sci. 2022, 23(15), 8138; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23158138 - 23 Jul 2022
Cited by 1 | Viewed by 1888
Abstract
Despite emerging evidence suggesting that autophagy occurs during renal interstitial fibrosis, the role of autophagy activation in fibrosis and the mechanism by which autophagy influences fibrosis remain controversial. Transcription factor EB (TFEB) is a master regulator of autophagy-related gene transcription, lysosomal biogenesis, and [...] Read more.
Despite emerging evidence suggesting that autophagy occurs during renal interstitial fibrosis, the role of autophagy activation in fibrosis and the mechanism by which autophagy influences fibrosis remain controversial. Transcription factor EB (TFEB) is a master regulator of autophagy-related gene transcription, lysosomal biogenesis, and autophagosome formation. In this study, we examined the preventive effects of TFEB suppression on renal fibrosis. We injected synthesized TFEB decoy oligonucleotides (ODNs) into the tail veins of unilateral ureteral obstruction (UUO) mice to explore the regulation of autophagy in UUO-induced renal fibrosis. The expression of interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), and collagen was decreased by TFEB decoy ODN. Additionally, TEFB ODN administration inhibited the expression of microtubule-associated protein light chain 3 (LC3), Beclin1, and hypoxia-inducible factor-1α (HIF-1α). We confirmed that TFEB decoy ODN inhibited fibrosis and autophagy in a UUO mouse model. The TFEB decoy ODNs also showed anti-inflammatory effects. Collectively, these results suggest that TFEB may be involved in the regulation of autophagy and fibrosis and that regulating TFEB activity may be a promising therapeutic strategy against kidney diseases. Full article
(This article belongs to the Special Issue Fibrosis-Related lncRNA)
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Review

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25 pages, 2345 KiB  
Review
Pathogenic Roles of Autoantibodies and Aberrant Epigenetic Regulation of Immune and Connective Tissue Cells in the Tissue Fibrosis of Patients with Systemic Sclerosis
by Chang-Youh Tsai, Song-Chou Hsieh, Tsai-Hung Wu, Ko-Jen Li, Chieh-Yu Shen, Hsien-Tzung Liao, Cheng-Han Wu, Yu-Min Kuo, Cheng-Shiun Lu and Chia-Li Yu
Int. J. Mol. Sci. 2020, 21(9), 3069; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21093069 - 27 Apr 2020
Cited by 14 | Viewed by 3776
Abstract
Systemic sclerosis (SSc) is a multi-system autoimmune disease with tissue fibrosis prominent in the skin and lung. In this review, we briefly describe the autoimmune features (mainly autoantibody production and cytokine profiles) and the potential pathogenic contributors including genetic/epigenetic predisposition, and environmental factors. [...] Read more.
Systemic sclerosis (SSc) is a multi-system autoimmune disease with tissue fibrosis prominent in the skin and lung. In this review, we briefly describe the autoimmune features (mainly autoantibody production and cytokine profiles) and the potential pathogenic contributors including genetic/epigenetic predisposition, and environmental factors. We look in detail at the cellular and molecular bases underlying tissue-fibrosis which include trans-differentiation of fibroblasts (FBs) to myofibroblasts (MFBs). We also state comprehensively the pro-inflammatory and pro-fibrotic cytokines relevant to MFB trans-differentiation, vasculopathy-associated autoantibodies, and fibrosis-regulating microRNAs in SSc. It is conceivable that tissue fibrosis is mainly mediated by an excessive production of TGF-β, the master regulator, from the skewed Th2 cells, macrophages, fibroblasts, myofibroblasts, and keratinocytes. After binding with TGF-β receptors on MFB, the downstream Wnt/β-catenin triggers canonical Smad 2/3 and non-canonical Smad 4 signaling pathways to transcribe collagen genes. Subsequently, excessive collagen fiber synthesis and accumulation as well as tissue fibrosis ensue. In the later part of this review, we discuss limited data relevant to the role of long non-coding RNAs (lncRNAs) in tissue-fibrosis in SSc. It is expected that these lncRNAs may become the useful biomarkers and therapeutic targets for SSc in the future. The prospective investigations in the development of novel epigenetic modifiers are also suggested. Full article
(This article belongs to the Special Issue Fibrosis-Related lncRNA)
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16 pages, 333 KiB  
Review
LncRNAs Act as a Link between Chronic Liver Disease and Hepatocellular Carcinoma
by Young-Ah Kim, Kwan-Kyu Park and Sun-Jae Lee
Int. J. Mol. Sci. 2020, 21(8), 2883; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21082883 - 20 Apr 2020
Cited by 20 | Viewed by 2655
Abstract
Long non-coding RNAs (lncRNAs) are emerging as important contributors to the biological processes underlying the pathophysiology of various human diseases, including hepatocellular carcinoma (HCC). However, the involvement of these molecules in chronic liver diseases, such as nonalcoholic fatty liver disease (NAFLD) and viral [...] Read more.
Long non-coding RNAs (lncRNAs) are emerging as important contributors to the biological processes underlying the pathophysiology of various human diseases, including hepatocellular carcinoma (HCC). However, the involvement of these molecules in chronic liver diseases, such as nonalcoholic fatty liver disease (NAFLD) and viral hepatitis, has only recently been considered in scientific research. While extensive studies on the pathogenesis of the development of HCC from hepatic fibrosis have been conducted, their regulatory molecular mechanisms are still only partially understood. The underlying mechanisms related to lncRNAs leading to HCC from chronic liver diseases and cirrhosis have not yet been entirely elucidated. Therefore, elucidating the functional roles of lncRNAs in chronic liver disease and HCC can contribute to a better understanding of the molecular mechanisms, and may help in developing novel diagnostic biomarkers and therapeutic targets for HCC, as well as in preventing the progression of chronic liver disease to HCC. Here, we comprehensively review and briefly summarize some lncRNAs that participate in both hepatic fibrosis and HCC. Full article
(This article belongs to the Special Issue Fibrosis-Related lncRNA)
14 pages, 530 KiB  
Review
Potential Roles of Long Noncoding RNAs as Therapeutic Targets in Renal Fibrosis
by Hyun Jin Jung, Hyun-Ju Kim and Kwan-Kyu Park
Int. J. Mol. Sci. 2020, 21(8), 2698; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21082698 - 13 Apr 2020
Cited by 14 | Viewed by 2677
Abstract
Many studies have made clear that most of the genome is transcribed into noncoding RNAs, including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), both of which can affect different cell features. LncRNAs are long heterogeneous RNAs that regulate gene expression and a variety [...] Read more.
Many studies have made clear that most of the genome is transcribed into noncoding RNAs, including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), both of which can affect different cell features. LncRNAs are long heterogeneous RNAs that regulate gene expression and a variety of signaling pathways involved in cellular homeostasis and development. Several studies have demonstrated that lncRNA is an important class of regulatory molecule that can be targeted to change cellular physiology and function. The expression or dysfunction of lncRNAs is closely related to various hereditary, autoimmune, and metabolic diseases, and tumors. Specifically, recent work has shown that lncRNAs have an important role in kidney pathogenesis. The effective roles of lncRNAs have been recognized in renal ischemia, injury, inflammation, fibrosis, glomerular diseases, renal transplantation, and renal-cell carcinoma. The present review focuses on the emerging role and function of lncRNAs in the pathogenesis of kidney inflammation and fibrosis as novel essential regulators. Although lncRNAs are important players in the initiation and progression of many pathological processes, their role in renal fibrosis remains unclear. This review summarizes the current understanding of lncRNAs in the pathogenesis of kidney fibrosis and elucidates the potential role of these novel regulatory molecules as therapeutic targets for the clinical treatment of kidney inflammation and fibrosis. Full article
(This article belongs to the Special Issue Fibrosis-Related lncRNA)
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19 pages, 1705 KiB  
Review
The Roles and Mechanisms of lncRNAs in Liver Fibrosis
by Zhi He, Deying Yang, Xiaolan Fan, Mingwang Zhang, Yan Li, Xiaobin Gu and Mingyao Yang
Int. J. Mol. Sci. 2020, 21(4), 1482; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21041482 - 21 Feb 2020
Cited by 70 | Viewed by 6565
Abstract
Many studies have revealed that circulating long noncoding RNAs (lncRNAs) regulate gene and protein expression in the process of hepatic fibrosis. Liver fibrosis is a reversible wound healing response followed by excessive extracellular matrix accumulation. In the development of liver fibrosis, some lncRNAs [...] Read more.
Many studies have revealed that circulating long noncoding RNAs (lncRNAs) regulate gene and protein expression in the process of hepatic fibrosis. Liver fibrosis is a reversible wound healing response followed by excessive extracellular matrix accumulation. In the development of liver fibrosis, some lncRNAs regulate diverse cellular processes by acting as competing endogenous RNAs (ceRNAs) and binding proteins. Previous investigations demonstrated that overexpression of lncRNAs such as H19, maternally expressed gene 3 (MEG3), growth arrest-specific transcript 5 (GAS5), Gm5091, NR_002155.1, and HIF 1alpha-antisense RNA 1 (HIF1A-AS1) can inhibit the progression of liver fibrosis. Furthermore, the upregulation of several lncRNAs [e.g., nuclear paraspeckle assembly transcript 1 (NEAT1), hox transcript antisense RNA (Hotair), and liver-enriched fibrosis-associated lncRNA1 (lnc-LFAR1)] has been reported to promote liver fibrosis. This review will focus on the functions and mechanisms of lncRNAs, the lncRNA transcriptome profile of liver fibrosis, and the main lncRNAs involved in the signalling pathways that regulate hepatic fibrosis. This review provides insight into the screening of therapeutic and diagnostic markers of liver fibrosis. Full article
(This article belongs to the Special Issue Fibrosis-Related lncRNA)
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19 pages, 2599 KiB  
Review
Idiopathic Pulmonary Fibrosis: Pathogenesis and the Emerging Role of Long Non-Coding RNAs
by Marina R. Hadjicharalambous and Mark A. Lindsay
Int. J. Mol. Sci. 2020, 21(2), 524; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21020524 - 14 Jan 2020
Cited by 42 | Viewed by 13622
Abstract
Idiopathic pulmonary fibrosis (IPF) is a progressive chronic disease characterized by excessing scarring of the lungs leading to irreversible decline in lung function. The aetiology and pathogenesis of the disease are still unclear, although lung fibroblast and epithelial cell activation, as well as [...] Read more.
Idiopathic pulmonary fibrosis (IPF) is a progressive chronic disease characterized by excessing scarring of the lungs leading to irreversible decline in lung function. The aetiology and pathogenesis of the disease are still unclear, although lung fibroblast and epithelial cell activation, as well as the secretion of fibrotic and inflammatory mediators, have been strongly associated with the development and progression of IPF. Significantly, long non-coding RNAs (lncRNAs) are emerging as modulators of multiple biological processes, although their function and mechanism of action in IPF is poorly understood. LncRNAs have been shown to be important regulators of several diseases and their aberrant expression has been linked to the pathophysiology of fibrosis including IPF. This review will provide an overview of this emerging role of lncRNAs in the development of IPF. Full article
(This article belongs to the Special Issue Fibrosis-Related lncRNA)
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