miR-223:A Key Regulator in the Innate Immune Response in Asthma and COPD

Asthma and Chronic Obstructive Pulmonary Disease (COPD) are chronic obstructive respiratory diseases characterized by airway obstruction, inflammation, and remodeling. Recent findings indicate the importance of microRNAs (miRNAs) in the regulation ofpathological processes involved in both diseases. MiRNAs have been implicated in a wide array of biological processes, such as inflammation, cell proliferation, differentiation, and death. MiR-223 is one of the miRNAs that is thought to play a role in obstructive lung disease as altered expression levels have been observed in both asthma and COPD. MiR-223 is a hematopoietic cell–derived miRNA that plays a role in regulation of monocyte-macrophage differentiation, neutrophil recruitment, and pro-inflammatory responses and that can be transferred to non-myeloid cells via extracellular vesicles or lipoproteins. In this translational review, we highlight the role of miR-223 in obstructive respiratory diseases, focusing on expression data in clinical samples of asthma and COPD, in vivo experiments in mouse models and in vitro functional studies. Furthermore, we provide an overview of the mechanisms by which miR-223 regulates gene expression. We specifically focus on immune cell development and activation and involvement in immune responses, which are important in asthma and COPD. Collectively, this review demonstrates the importance of miR-223 in obstructive respiratory diseases and explores its therapeutic potential in the pathogenesis of asthma and COPD. <br/

miR-223 : a key regulator in the innate immune response in asthma and COPD

Asthma and Chronic Obstructive Pulmonary Disease (COPD) are chronic obstructive respiratory diseases characterized by airway obstruction, inflammation, and remodeling. Recent findings indicate the importance of microRNAs (miRNAs) in the regulation of pathological processes involved in both diseases. MiRNAs have been implicated in a wide array of biological processes, such as inflammation, cell proliferation, differentiation, and death. MiR-223 is one of the miRNAs that is thought to play a role in obstructive lung disease as altered expression levels have been observed in both asthma and COPD. MiR-223 is a hematopoietic cell-derived miRNA that plays a role in regulation of monocyte-macrophage differentiation, neutrophil recruitment, and pro-inflammatory responses and that can be transferred to non-myeloid cells via extracellular vesicles or lipoproteins. In this translational review, we highlight the role of miR-223 in obstructive respiratory diseases, focusing on expression data in clinical samples of asthma and COPD, in vivo experiments in mouse models and in vitro functional studies. Furthermore, we provide an overview of the mechanisms by which miR-223 regulates gene expression. We specifically focus on immune cell development and activation and involvement in immune responses, which are important in asthma and COPD. Collectively, this review demonstrates the importance of miR-223 in obstructive respiratory diseases and explores its therapeutic potential in the pathogenesis of asthma and COPD

Let’s Keep in Touch:Strong Cell-cell Contacts for Healthy Lungs

Prof Irene Heijink (1975) and her team study the mechanisms underlying lung tissue damage in various lung diseases, such as asthma, COPD and pulmonary fibrosis She does this in close collaboration with the clinic, using culture models with cells derived from patients. Heijink directs the Experimental Lung Diseases Lab (EXPIRE) and is currently programme leader of the Groningen Research Institute for COPD (GRIAC), a multidisciplinary and translational research institute in which close collaboration takes place between basic and clinical scientists.Lung diseases are a major social problem. Diseases such as asthma and COPD are common and have a major impact on quality of life. In fact, COPD is currently the third box cause worldwide. Lung diseases are often only detected at a late stage when there is already significant damage that is no longer treatable. In particular, damage to the lining layer of the airways and lungs (the epithelium - involved in immune processes) with loss of mutual contact between cells in this layer is currently seen as a crucial part of disease processes. Irene Heijink discovered that an important directing role is played by the damaged epithelium in the derailed inflammatory response in the lungs of asthma and COPD patients. In her Chair in Cellular and Molecular Lung Pathology, Heijink aims to develop new strategies to repair the epithelial barrier in lung diseases and thereby stop or even reverse the disease process. In doing so, she uses advanced culture models (such as lab-on-chip), which she is developing within a large national collaboration to detect lung damage earlier and find new leads for treatment. She is also developing a new strategy in collaboration with the University of Twente, using an innovative technology, to better treat damage deep in the lungs and possibly even achieve tissue repair

Effects of cigarette smoking on SARS-CoV-2 receptor ACE2 expression in the respiratory epithelium(dagger)

Due to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, the world is currently facing high morbidity and mortality rates as well as severe disruption to normal societal and social structures. SARS-CoV-2 uses the ACE2 receptor for cellular entry. In a recent publication of The Journal of Pathology, Liu and coworkers highlight the effects of cigarette smoking on ACE2 expression in the respiratory epithelium. The authors studied the effects of acute cigarette smoke exposure in a murine model and confirmed their findings in human lung tissues and gene expression datasets. Their findings demonstrate that cigarette smoking increases ACE2 expression specifically at the apical surface of the airway epithelium. Smoking cessation resulted in lower ACE2 expression, with implications for attenuating the risk of transmission of the virus. The role of ACE2 expression in the development of COVID-19 symptoms is still under investigation, with conflicting results from experimental models on the role of ACE2 expression in SARS-CoV-2-induced lung injury. In this commentary, we highlight the implications and limitations of the study of Liu et al as well as future therapeutic strategies directed towards ACE2. (c) 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland

Cell fate after DNA damage

Het is essentieel voor een cel om zijn genetische informatie onveranderd en intact door te geven aan zijn nageslacht. Toch ontstaan in elke cel per dag enkele tienduizenden beschadigingen aan het DNA. Om te voorkomen dat deze schade leidt tot blijvende veranderingen in het DNA, genaamd: “mutaties”, hebben cellen verschillende mechanismen ontwikkeld die samen ‘de DNA-schaderespons’ (DSR) wordt genoemd. De DSR zorgt er onder andere voor dat schade opgemerkt wordt, dat lopende processen in de cel tijdelijk stilgelegd worden, en de schade vervolgens gerepareerd wordt. Erfelijke mutaties in DNA-reparatiegenen BRCA1 en BRCA2, onderstrepen het belang van een functionele DNA-reparatiemachinerie. Vrouwen met een erfelijke mutatie in één van deze reparatiegenen hebben tot 70% kans op het ontwikkelen van borstkanker voor hun 70-ste levensjaar. Naast het feit dat defecten in DNA-reparatiegenen kanker kunnen veroorzaken, biedt de DSR ook mogelijkheden voor doelgerichte behandeling van tumorcellen. Wanneer een tumorcel bijvoorbeeld niet genoeg tijd krijgt om DNA-schade te repareren, kan de hoeveelheid schade zo groot worden dat de tumorcel een programma activeert om zichzelf uit te schakelen. Het doel van dit promotieonderzoek was om factoren en mechanismen te identificeren die het lot van kankercellen na DNA-schade bepalen. Specifiek werd onderzocht hoe cellen het verlies van een essentieel DNA-reparatiegen (BRCA2) kunnen overleven. Hiernaast is onderzocht op welke manieren tumorcellen celdood kunnen ontlopen na DNA-schade geïnduceerd door chemotherapie of remmers van de DSR. Er is gebleken dat er verschillende manieren zijn hoe tumorcellen DNA-schade overleven. Deze manieren vormen veel mogelijkheden voor doelgerichte therapieën, maar maken het voorspellen van de respons op therapieën moeilijk