Role of Non-Coding RNAs in Post-Transcriptional Regulation of Lung Diseases

Lung Diseases ◽

Fine Tuning ◽

Chronic Obstructive ◽

Biological Processes ◽

Non Coding Rnas ◽

Specific Tissue ◽

Post Transcriptional Regulation

Non-coding RNAs (ncRNAs), notably microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), have recently gained increasing consideration because of their versatile role as key regulators of gene expression. They adopt diverse mechanisms to regulate transcription and translation, and thereby, the function of the protein, which is associated with several major biological processes. For example, proliferation, differentiation, apoptosis, and metabolic pathways demand fine-tuning for the precise development of a specific tissue or organ. The deregulation of ncRNA expression is concomitant with multiple diseases, including lung diseases. This review highlights recent advances in the post-transcriptional regulation of miRNAs and lncRNAs in lung diseases such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, and idiopathic pulmonary fibrosis. Further, we also discuss the emerging role of ncRNAs as biomarkers as well as therapeutic targets for lung diseases. However, more investigations are required to explore miRNAs and lncRNAs interaction, and their function in the regulation of mRNA expression. Understanding these mechanisms might lead to early diagnosis and the development of novel therapeutics for lung diseases.

Aberrant Post-Transcriptional Regulation of Protein Expression in the Development of Chronic Obstructive Pulmonary Disease

International Journal of Molecular Sciences ◽

10.3390/ijms222111963 ◽

2021 ◽

Vol 22 (21) ◽

pp. 11963

Author(s):

Noof Aloufi ◽

Aeshah Alluli ◽

David H. Eidelman ◽

Carolyn J. Baglole

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Pulmonary Disease ◽

Rna Binding ◽

Rna Binding Proteins ◽

Chronic Obstructive ◽

Respiratory Disorder ◽

Cellular Processes ◽

Post Transcriptional Regulation

Chronic obstructive pulmonary disease (COPD) is an incurable and prevalent respiratory disorder that is characterized by chronic inflammation and emphysema. COPD is primarily caused by cigarette smoke (CS). CS alters numerous cellular processes, including the post-transcriptional regulation of mRNAs. The identification of RNA-binding proteins (RBPs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) as main factors engaged in the regulation of RNA biology opens the door to understanding their role in coordinating physiological cellular processes. Dysregulation of post-transcriptional regulation by foreign particles in CS may lead to the development of diseases such as COPD. Here we review current knowledge about post-transcriptional events that may be involved in the pathogenesis of COPD.

Smoking and interstitial lung diseases

European Respiratory Review ◽

10.1183/16000617.0050-2015 ◽

2015 ◽

Vol 24 (137) ◽

pp. 428-435 ◽

Cited By ~ 21

Author(s):

George A. Margaritopoulos ◽

Eirini Vasarmidi ◽

Joseph Jacob ◽

Athol U. Wells ◽

Katerina M. Antoniou

Keyword(s):

Lung Cancer ◽

Chronic Obstructive Pulmonary Disease ◽

Langerhans Cell Histiocytosis ◽

Lung Diseases ◽

Interstitial Lung Diseases ◽

Lung Damage ◽

Chronic Obstructive ◽

Pulmonary Langerhans Cell Histiocytosis

For many years has been well known that smoking could cause lung damage. Chronic obstructive pulmonary disease and lung cancer have been the two most common smoking-related lung diseases. In the recent years, attention has also focused on the role of smoking in the development of interstitial lung diseases (ILDs). Indeed, there are three diseases, namely respiratory bronchiolitis-associated ILD, desquamative interstitial pneumonia and pulmonary Langerhans cell histiocytosis, that are currently considered aetiologically linked to smoking and a few others which are more likely to develop in smokers. Here, we aim to focus on the most recent findings regarding the role of smoking in the pathogenesis and clinical behaviour of ILDs.

Role of N6-Methyladenosine RNA Modification in Cardiovascular Disease

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.659628 ◽

2021 ◽

Vol 8 ◽

Author(s):

Dandan Song ◽

Jianhua Hou ◽

Junduo Wu ◽

Junnan Wang

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Recent Progress ◽

Rna Modification ◽

Non Coding Rnas ◽

Post Transcriptional Regulation

Despite treatments being improved and many risk factors being identified, cardiovascular disease (CVD) is still a leading cause of mortality and disability worldwide. N6-methyladenosine (m6A) is the most common, abundant, and conserved internal modification in RNAs and plays an important role in the development of CVD. Many studies have shown that aabnormal m6A modifications of coding RNAs are involved in the development of CVD. In addition, non-coding RNAs (ncRNAs) exert post-transcriptional regulation in many diseases including CVD. Although ncRNAs have also been found to be modified by m6A, the studies on m6A modifications of ncRNAs in CVD are currently lacking. In this review, we summarized the recent progress in understanding m6A modifications in the context of coding RNAs and ncRNAs, as well as their regulatory roles in CVD.

Interleukin-36 Cytokines in Infectious and Non-Infectious Lung Diseases

Frontiers in Immunology ◽

10.3389/fimmu.2021.754702 ◽

2021 ◽

Vol 12 ◽

Author(s):

Hernán F. Peñaloza ◽

Rick van der Geest ◽

Joel A. Ybe ◽

Theodore J. Standiford ◽

Janet S. Lee

Keyword(s):

Infectious Diseases ◽

Lung Diseases ◽

Skin Diseases ◽

Inflammatory Diseases ◽

Lymphoid Cells ◽

Chronic Obstructive ◽

Inflammatory Conditions ◽

Inflammatory Processes

The IL-36 family of cytokines were identified in the early 2000’s as a new subfamily of the IL-1 cytokine family, and since then, the role of IL-36 cytokines during various inflammatory processes has been characterized. While most of the research has focused on the role of these cytokines in autoimmune skin diseases such as psoriasis and dermatitis, recent studies have also shown the importance of IL-36 cytokines in the lung inflammatory response during infectious and non-infectious diseases. In this review, we discuss the biology of IL-36 cytokines in terms of how they are produced and activated, as well as their effects on myeloid and lymphoid cells during inflammation. We also discuss the role of these cytokines during lung infectious diseases caused by bacteria and influenza virus, as well as other inflammatory conditions in the lungs such as allergic asthma, lung fibrosis, chronic obstructive pulmonary disease, cystic fibrosis and cancer. Finally, we discuss the current therapeutic advances that target the IL-36 pathway and the possibility to extend these tools to treat lung inflammatory diseases.

Differential plasma exosomal long non-coding RNAs expression profiles and their emerging role in E-cigarette users, cigarette, waterpipe, and dual smokers

PLoS ONE ◽

10.1371/journal.pone.0243065 ◽

2020 ◽

Vol 15 (12) ◽

pp. e0243065 ◽

Cited By ~ 1

Author(s):

Gagandeep Kaur ◽

Kameshwar Singh ◽

Krishna P. Maremanda ◽

Dongmei Li ◽

Hitendra S. Chand ◽

...

Keyword(s):

Expression Profiles ◽

Transcriptional Profiling ◽

Critical Role ◽

Cell Communication ◽

Chronic Obstructive ◽

Biological Processes ◽

Chronic Lung Diseases ◽

Non Coding Rnas ◽

Differentiation And Proliferation

Long non-coding RNAs (lncRNAs) are the varied set of transcripts that play a critical role in biological processes like gene regulation, transcription, post-transcriptional modification, and chromatin remodeling. Recent studies have reported the presence of lncRNAs in the exosomes that are involved in regulating cell-to-cell communication in lung pathologies including lung cancer, chronic obstructive pulmonary disease (COPD), asthma, and idiopathic pulmonary fibrosis (IPF). In this study, we compared the lncRNA profiles in the plasma-derived exosomes amongst non-smokers (NS), cigarette smokers (CS), E-cig users (E-cig), waterpipe smokers (WP) and dual smokers (CSWP) using GeneChip™ WT Pico kit for transcriptional profiling. We found alterations in a distinct set of lncRNAs among subjects exposed to E-cig vapor, cigarette smoke, waterpipe smoke and dual smoke with some overlaps. Gene enrichment analyses of the differentially expressed lncRNAs demonstrated enrichment in the lncRNAs involved in crucial biological processes including steroid metabolism, cell differentiation and proliferation. Thus, the characterized lncRNA profiles of the plasma-derived exosomes from smokers, vapers, waterpipe users, and dual smokers will help identify the biomarkers relevant to chronic lung diseases such as COPD, asthma or IPF.

Use of nonhuman primates in obstructive lung disease research – is it required?

Primate Biology ◽

10.5194/pb-4-131-2017 ◽

2017 ◽

Vol 4 (1) ◽

pp. 131-142

Author(s):

Franziska Dahlmann ◽

Katherina Sewald

Keyword(s):

Obstructive Lung Disease ◽

Lung Diseases ◽

Nonhuman Primates ◽

Animal Experiments ◽

Alternative Methods ◽

Chronic Obstructive ◽

Therapeutic Approaches ◽

Disease Research

Abstract. In times of increasing costs for health insurances, obstructive lung diseases are a burden for both the patients and the economy. Pulmonary symptoms of asthma and chronic obstructive pulmonary disease (COPD) are similar; nevertheless, the diseases differ in pathophysiology and therapeutic approaches. Novel therapeutics are continuously developed, and nonhuman primates (NHPs) provide valuable models for investigating novel biologicals regarding efficacy and safety.This review discusses the role of nonhuman primate models for drug development in asthma and COPD and investigates whether alternative methods are able to prevent animal experiments.

MicroRNAs: Beyond Post-transcriptional Regulation of mRNAs

MicroRNA ◽

10.2174/2211536611666211228102045 ◽

2021 ◽

Vol 11 ◽

Author(s):

Cervantes-Ayala Andrea Viridiana ◽

Velázquez-Flores Miguel Ángel ◽

Ruiz Esparza-Garrido Ruth

Keyword(s):

Mature Mirnas ◽

Regulatory Function ◽

Biological Processes ◽

Nuclear Level ◽

Eukaryotic Genes ◽

Non Coding Rnas ◽

Post Transcriptional Regulation ◽

Potential Biomarkers

Abstract: MicroRNAs (miRNAs), small non-coding RNAs, participate in the transcriptional and post-transcriptional regulation of eukaryotic genes, and are potential biomarkers for diseases. Mature miRNAs can be located in both the nucleus and cytoplasm, where they perform their regulatory function. The discovery of new miRNAs and the identification of their targets and functions are fundamental to understanding the biological processes regulated by them, as well as the role they play in diseases. This present study researched miRNAs function at nuclear level and as circulating molecules.

Genetically manipulated mouse models of lung disease: potential and pitfalls

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00085.2011 ◽

2012 ◽

Vol 302 (6) ◽

pp. L485-L497 ◽

Cited By ~ 41

Author(s):

Rebecca M. Baron ◽

Alexander J. S. Choi ◽

Caroline A. Owen ◽

Augustine M. K. Choi

Keyword(s):

Lung Disease ◽

Lung Diseases ◽

Genetically Engineered ◽

Chronic Obstructive ◽

Biological Processes ◽

Molecular Events ◽

Genetically Engineered Mice ◽

Genetically Manipulated ◽

Parenchymal Lung

Gene targeting in mice (transgenic and knockout) has provided investigators with an unparalleled armamentarium in recent decades to dissect the cellular and molecular basis of critical pathophysiological states. Fruitful information has been derived from studies using these genetically engineered mice with significant impact on our understanding, not only of specific biological processes spanning cell proliferation to cell death, but also of critical molecular events involved in the pathogenesis of human disease. This review will focus on the use of gene-targeted mice to study various models of lung disease including airways diseases such as asthma and chronic obstructive pulmonary disease, and parenchymal lung diseases including idiopathic pulmonary fibrosis, pulmonary hypertension, pneumonia, and acute lung injury. We will attempt to review the current technological approaches of generating gene-targeted mice and the enormous dataset derived from these studies, providing a template for lung investigators.

Dysregulation of the glutaredoxin/S-glutathionylation redox axis in lung diseases

AJP Cell Physiology ◽

10.1152/ajpcell.00410.2019 ◽

2020 ◽

Vol 318 (2) ◽

pp. C304-C327 ◽

Cited By ~ 4

Author(s):

Shi B. Chia ◽

Evan A. Elko ◽

Reem Aboushousha ◽

Allison M. Manuel ◽

Cheryl van de Wetering ◽

...

Keyword(s):

Lung Diseases ◽

Defense Mechanism ◽

Protein S ◽

Chronic Obstructive ◽

Mixed Disulfide ◽

Glutathione S Transferases ◽

And Function ◽

Redox Buffer

Glutathione is a major redox buffer, reaching millimolar concentrations within cells and high micromolar concentrations in airways. While glutathione has been traditionally known as an antioxidant defense mechanism that protects the lung tissue from oxidative stress, glutathione more recently has become recognized for its ability to become covalently conjugated to reactive cysteines within proteins, a modification known as S-glutathionylation (or S-glutathiolation or protein mixed disulfide). S-glutathionylation has the potential to change the structure and function of the target protein, owing to its size (the addition of three amino acids) and charge (glutamic acid). S-glutathionylation also protects proteins from irreversible oxidation, allowing them to be enzymatically regenerated. Numerous enzymes have been identified to catalyze the glutathionylation/deglutathionylation reactions, including glutathione S-transferases and glutaredoxins. Although protein S-glutathionylation has been implicated in numerous biological processes, S-glutathionylated proteomes have largely remained unknown. In this paper, we focus on the pathways that regulate GSH homeostasis, S-glutathionylated proteins, and glutaredoxins, and we review methods required toward identification of glutathionylated proteomes. Finally, we present the latest findings on the role of glutathionylation/glutaredoxins in various lung diseases: idiopathic pulmonary fibrosis, asthma, and chronic obstructive pulmonary disease.

The Role of Connexin 43 in Lung Disease

Life ◽

10.3390/life10120363 ◽

2020 ◽

Vol 10 (12) ◽

pp. 363

Author(s):

Julie A. Swartzendruber ◽

Bruce J. Nicholson ◽

Ashlesh K. Murthy

Keyword(s):

Lung Disease ◽

Lung Diseases ◽

Connexin 43 ◽

Distress Syndrome ◽

Cell Types ◽

Mortality Rates ◽

Chronic Obstructive ◽

Junction Proteins

The term lung disease describes a broad category of disorders that impair lung function. More than 35 million Americans have a preventable chronic lung disease with high mortality rates due to limited treatment efficacy. The recent increase in patients with lung disease highlights the need to increase our understanding of mechanisms driving lung inflammation. Connexins, gap junction proteins, and more specifically connexin 43 (Cx43), are abundantly expressed in the lung and are known to play a role in lung diseases. This review focuses on the role of Cx43 in pathology associated with acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD) and asthma. Additionally, we discuss the role of Cx43 in preventing disease through the transfer of mitochondria between cells. We aim to highlight the need to better understand what cell types are expressing Cx43 and how this expression influences lung disease.