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Alveolar epithelial repair

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https://www.readbyqxmd.com/read/28428174/klotho-an-anti-aging-molecule-attenuates-oxidant-induced-alveolar-epithelial-cell-mtdna-damage-and-apoptosis
#1
Seok-Jo Kim, Paul Cheresh, Mesut Eren, Renea P Jablonski, Anjana Yeldandi, Karen M Ridge, Gr Scott Budinger, Dong-Hyun Kim, Myles S Wolf, Douglas Vaughan, David W Kamp
Alveolar epithelial cell (AEC) apoptosis and inadequate repair resulting from 'exaggerated' lung aging and mitochondrial dysfunction are critical determinants promoting lung fibrosis. α-Klotho, which is an anti-aging molecule that is expressed predominantly in the kidney and secreted in the blood, can protect lung epithelial cells against hyperoxia-induced apoptosis. We reasoned that Klotho protects AEC exposed to oxidative stress in part by maintaining mitochondrial DNA (mtDNA) integrity and mitigating apoptosis...
April 20, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28417017/galectin-1-inhibition-attenuates-profibrotic-signaling-in-hypoxia-induced-pulmonary-fibrosis
#2
Jaymin J Kathiriya, Niyati Nakra, Jenna Nixon, Puja S Patel, Vijay Vaghasiya, Ahmed Alhassani, Zhi Tian, Diane Allen-Gipson, Vrushank Davé
Idiopathic pulmonary fibrosis (IPF) is characterized by lung remodeling arising from epithelial injury, aberrant fibroblast growth, and excessive deposition of extracellular matrix. Repeated epithelial injury elicits abnormal wound repair and lung remodeling, often associated with alveolar collapse and edema, leading to focal hypoxia. Here, we demonstrate that hypoxia is a physiological insult that contributes to pulmonary fibrosis (PF) and define its molecular roles in profibrotic activation of lung epithelial cells...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28402849/uroplakin-3a-cells-are-a-distinctive-population-of-epithelial-progenitors-that-contribute-to-airway-maintenance-and-post-injury-repair
#3
Arjun Guha, Aditya Deshpande, Aradhya Jain, Paola Sebastiani, Wellington V Cardoso
There is evidence that certain club cells (CCs) in the murine airways associated with neuroepithelial bodies (NEBs) and terminal bronchioles are resistant to the xenobiotic naphthalene (Nap) and repopulate the airways after Nap injury. The identity and significance of these progenitors (variant CCs, v-CCs) have remained elusive. A recent screen for CC markers identified rare Uroplakin3a (Upk3a)-expressing cells (U-CCs) with a v-CC-like distribution. Here, we employ lineage analysis in the uninjured and chemically injured lungs to investigate the role of U-CCs as epithelial progenitors...
April 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28370323/recombinant-cells-in-the-lung-increase-with-age-via-de-novo-recombination-events-and-clonal-expansion
#4
Takafumi Kimoto, Jennifer E Kay, Na Li, Bevin P Engelward
Homologous recombination (HR) is a critical DNA repair pathway, which is usually error-free, but can sometimes lead to cancer-promoting mutations. Despite the importance of HR as a driver of mutations, the spontaneous frequency of such mutations has proven difficult to study. To gain insight to location, cell type, and subsequent proliferation of mutated cells, we used the Rosa26 Direct Repeat (RaDR) mice for in situ detection and quantification of recombinant cells in the lung. We developed a method for automated enumeration of recombinant cells in lung tissue using the Metafer 4 slide-scanning platform...
April 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28360109/focal-adhesion-kinase-signaling-determines-the-fate-of-lung-epithelial-cells-in-response-to-tgf-%C3%AE
#5
Qiang Ding, Indhu Subramanian, Tracy R Luckhardt, Pulin Che, Meghna Waghray, Xueke Zhao, Nathaniel Bone, Ashish R Kurundkar, Louise Hecker, Meng Hu, Yong Zhou, Jeffrey Craig Horowitz, Ragini Vittal, Victor J Thannickal
Alveolar epithelial cell (AEC) injury and apoptosis are prominent pathological features of idiopathic pulmonary fibrosis (IPF). There is evidence of AEC plasticity in lung injury repair responses and in IPF. In this report, we explore the role of focal adhesion kinase (FAK) signaling in determining the fate of lung epithelial cells in response to TGF-β1. Rat type II alveolar epithelial cells (RLE-6TN) were treated with or without TGF-β1, and the expression of mesenchymal phenotype and function were analyzed...
March 30, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28339038/lncrna%C3%A2-mediated-sirt1-foxo3a-and-sirt1-p53-signaling-pathways-regulate-type-ii-alveolar-epithelial-cell-senescence-in-patients-with-chronic-obstructive-pulmonary-disease
#6
Chao Gu, Yaqing Li, Jialiang Liu, Xiwang Ying, Yuanshun Liu, Jianping Yan, Chun Chen, Hongbin Zhou, Liming Cao, Yingyu Ma
The loss of alveolar structure and airspace enlargement are major pathological changes in chronic obstructive pulmonary disease (COPD). Type II alveolar epithelial cells (AECII) are involved in maintaining lung tissue repair and alveolar homeostasis. Long non‑coding RNAs (lncRNAs) are involved in multi‑regulating gene transcription, affecting processes including embryonic development, cell differentiation and cellular senescence. The primary aim of the present study was to explore the mechanisms of AECII senescence regulated by lncRNA‑mediated sirtuin 1 (SIRT1) and forkhead box O 3a (FoxO3a) signaling pathways in patients with COPD...
May 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28333899/-stem-progenitor-cells-in-diseases-of-the-respiratory-tract
#7
EDITORIAL
Tadeusz Płusa
Stem cells (SCs - stem cells) are characterized by plasticity and the ability to differentiate into other cell types. They are obtained from bone marrow, peripheral blood and cord blood. Mesenchymal stem cells (MSCs) shows a broad immunomodulating, increases the number of regulatory T cells (Treg), modifies the activity of T cells, dendritic cells and NK (natural killer). Direct impact on reducing the release of proinflammatory cytokines and increased release of proinflammatory cytokines. Within the respiratory tract has a number of resident stem and progenitor cells referred to as L-MSCs (lung mesenchymal stem cells) whose presence was confirmed by markers as defined in the trachea, epithelial cells and alveolar...
March 21, 2017: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/28314802/an-ex-vivo-model-to-induce-early-fibrosis-like-changes-in-human-precision-cut-lung-slices
#8
Hani N Alsafadi, Claudia A Staab-Weijnitz, Mareike Lehmann, Michael Lindner, Britta Peschel, Melanie Königshoff, Darcy Elizabeth Wagner
IPF is a devastating chronic interstitial lung disease (ILD) characterized by lung tissue scarring and high morbidity. Lung epithelial injury, myofibroblast activation, and deranged repair are believed to be key processes involved in disease onset and progression but the exact molecular mechanisms behind IPF remain unclear. Several drugs have been shown to slow disease progression, but treatments which halt or reverse IPF progression have not been identified. Ex vivo models of human lung have been proposed for drug discovery, one of which is precision-cut lung slices (PCLS)...
March 17, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28296468/foxp3-regulatory-t-cell-expression-of-keratinocyte-growth-factor-enhances-lung-epithelial-proliferation
#9
Catherine F Dial, Miriya K Tune, Claire M Doerschuk, Jason R Mock
Repair of the lung epithelium after injury is a critical component for resolution; however, the processes necessary to drive epithelial resolution are not clearly defined. Published data demonstrate that Foxp3+ regulatory T cells (Tregs) enhance alveolar epithelial proliferation after injury, and Tregs in vitro directly promote type II alveolar epithelial cell (AT2) proliferation in part by a contact-independent mechanism. Therefore, we sought to determine the contribution of Treg-specific expression of a growth factor, keratinocyte growth factor (Kgf), known to be important in lung repair...
March 15, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28245136/reduced-frizzled-receptor-4-expression-prevents-wnt-%C3%AE-catenin-driven-alveolar-lung-repair-in-copd
#10
Wioletta Skronska-Wasek, Kathrin Mutze, Hoeke A Baarsma, Ken R Bracke, Hani N Alsafadi, Mareike Lehmann, Rita Costa, Mariano Stornaiuolo, Ettore Novellino, Guy G Brusselle, Darcy E Wagner, Ali Ö Yildirim, Melanie Königshoff
RATIONALE: Chronic obstructive pulmonary disease (COPD), in particular emphysema, is characterized by loss of parenchymal alveolar tissue and impaired tissue repair. WNT/β-catenin signaling is reduced in COPD, however, the mechanisms thereof, specifically the role of WNT receptors Frizzled (FZD), remains unexplored. OBJECTIVE: To identify and functionally characterize specific FZD receptors that control downstream WNT signaling in impaired lung repair in COPD. METHODS: FZD receptor expression was analyzed in lung homogenates and primary alveolar epithelial type II (ATII) cells of never-smokers, smokers, and COPD patients, as well as two experimental emphysema models by qRT-PCR, immunoblotting, and immunofluorescence...
February 28, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28237967/heterozygous-vangl2-looptail-mice-reveal-novel-roles-for-the-planar-cell-polarity-pathway-in-adult-lung-homeostasis-and-repair
#11
Thanushiyan Poobalasingam, Laura L Yates, Simone A Walker, Miguel Pereira, Nina Y Gross, Akmol Ali, Maria Kolatsi-Joannou, Marjo-Riitta Jarvelin, Juha Pekkanen, Eugenia Papakrivopoulou, David A Long, Mark Griffiths, Darcy Wagner, Melanie Königshoff, Matthew Hind, Cosetta Minelli, Clare M Lloyd, Charlotte H Dean
Lung diseases impose a huge economic and health burden worldwide. A key aspect of several adult lung diseases, such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD), including emphysema, is aberrant tissue repair, which leads to an accumulation of damage and impaired respiratory function. Currently, there are few effective treatments available for these diseases and their incidence is rising. The planar cell polarity (PCP) pathway is critical for the embryonic development of many organs, including kidney and lung...
April 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28193481/epigenetic-and-transcriptomic-regulation-of-lung-repair-during-recovery-from-influenza-infection
#12
Derek A Pociask, Keven M Robinson, Kong Chen, Kevin J McHugh, Michelle E Clay, Grace T Huang, Panayiotis V Benos, Yvonne M W Janssen-Heininger, Jay K Kolls, Vikas Anathy, John F Alcorn
Seasonal and pandemic influenza is a cause of morbidity and mortality worldwide. Most people infected with influenza virus display mild-to-moderate disease phenotypes and recover within a few weeks. Influenza is known to cause persistent alveolitis in animal models; however, little is known about the molecular pathways involved in this phenotype. We challenged C57BL/6 mice with influenza A/PR/8/34 and examined lung pathologic processes and inflammation, as well as transcriptomic and epigenetic changes at 21 to 60 days after infection...
April 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28157203/hepatocyte-growth-factor-secreted-by-bone-marrow-stem-cell-reduce-er-stress-and-improves-repair-in-alveolar-epithelial-ii-cells
#13
Izabela Nita, Katrin Hostettler, Luca Tamo, Michaela Medová, Giuseppe Bombaci, Jun Zhong, Ramanjaneyulu Allam, Yitzhak Zimmer, Michael Roth, Thomas Geiser, Amiq Gazdhar
Idiopathic Pulmonary Fibrosis (IPF) is a progressive, irreversible lung disease with complex pathophysiology. Evidence of endoplasmic reticulum (ER) stress has been reported in alveolar epithelial cells (AEC) in IPF patients. Secreted mediators from bone marrow stem cells (BMSC-cm) have regenerative properties. In this study we investigate the beneficial effects of BMSC-cm on ER stress response in primary AEC and ER stressed A549 cells. We hypothesize that BMSC-cm reduces ER stress. Primary AEC isolated from IPF patients were treated with BMSC-cm...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28151947/lung-protection-by-inhalation-of-exogenous-solubilized-extracellular-matrix
#14
Jinglei Wu, Priya Ravikumar, Kytai T Nguyen, Connie C W Hsia, Yi Hong
Decellularized extracellular matrix (ECM) contains complex tissue-specific components that work in concert to promote tissue repair and constructive remodeling and has been used experimentally and clinically to accelerate epithelial wound repair, leading us to hypothesize that lung-derived ECM could mitigate acute lung injury. To explore the therapeutic potential of ECM for noninvasive delivery to the lung, we decellularized and solubilized porcine lung ECM, then characterized the composition, concentration, particle size and stability of the preparation...
2017: PloS One
https://www.readbyqxmd.com/read/28128362/differentiation-of-club-cells-to-alveolar-epithelial-cells-in-vitro
#15
Dahai Zheng, Boon-Seng Soh, Lu Yin, Guangan Hu, Qingfeng Chen, Hyungwon Choi, Jongyoon Han, Vincent T K Chow, Jianzhu Chen
Club cells are known to function as regional progenitor cells to repair the bronchiolar epithelium in response to lung damage. By lineage tracing in mice, we have shown recently that club cells also give rise to alveolar type 2 cells (AT2s) and alveolar type 1 cells (AT1s) during the repair of the damaged alveolar epithelium. Here, we show that when highly purified, anatomically and phenotypically confirmed club cells are seeded in 3-dimensional culture either in bulk or individually, they proliferate and differentiate into both AT2- and AT1-like cells and form alveolar-like structures...
January 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28087752/deficient-retinoid-driven-angiogenesis-may-contribute-to-failure-of-adult-human-lung-regeneration-in-emphysema
#16
John-Poul Ng-Blichfeldt, Joana Alçada, M Angeles Montero, Charlotte H Dean, Uta Griesenbach, Mark J Griffiths, Matthew Hind
BACKGROUND: Molecular pathways that regulate alveolar development and adult repair represent potential therapeutic targets for emphysema. Signalling via retinoic acid (RA), derived from vitamin A, is required for mammalian alveologenesis, and exogenous RA can induce alveolar regeneration in rodents. Little is known about RA signalling in the human lung and its potential role in lung disease. OBJECTIVES: To examine regulation of human alveolar epithelial and endothelial repair by RA, and characterise RA signalling in human emphysema...
January 13, 2017: Thorax
https://www.readbyqxmd.com/read/28062913/understanding-the-developmental-pathways-pulmonary-fibroblasts-may-follow-during-alveolar-regeneration
#17
REVIEW
Stephen McGowan
Although pulmonary alveolar interstitial fibroblasts are less specialized than their epithelial and endothelial neighbors, they play essential roles during development and in response to lung injury. At birth, they must adapt to the sudden mechanical changes imposed by the onset of respiration and to a higher ambient oxygen concentration. In diseases such as bronchopulmonary dysplasia and interstitial fibrosis, their adaptive responses are overwhelmed leading to compromised gas-exchange function. Thus, although fibroblasts do not directly participate in gas-exchange, they are essential for creating and maintaining an optimal environment at the alveolar epithelial-endothelial interface...
March 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28044311/effects-of-hypercapnia-on-the-lung
#18
Masahiko Shigemura, Emilia Lecuona, Jacob I Sznajder
Gases are sensed by lung cells and can activate specific intracellular signalling pathways, and thus have physiological and pathophysiological effects. Carbon dioxide (CO2 ), a primary product of oxidative metabolism, can be sensed by eukaryotic cells eliciting specific responses via recently identified signalling pathways. However, the physiological and pathophysiological effects of high CO2 (hypercapnia) on the lungs and specific lung cells, which are the primary site of CO2 elimination, are incompletely understood...
April 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28028929/molecular-genetic-and-biochemical-responses-in-human-airway-epithelial-cell-cultures-exposed-to-titanium-nanoparticles-in-vitro
#19
Elanur Aydın, Hasan Türkez, Fazıl Hacımüftüoğlu, Abdulgani Tatar, Fatime Geyikoğlu
Titanium nanoparticles (NPs) have very wide application areas such as paint, cosmetics, pharmaceuticals and biomedical applications. And, to translate these nanomaterials to the clinic and industrial domains, their safety needs to be verified, particularly in terms of genotoxicity and cytotoxicity. Therefore, in this study, we aimed to investigate of cytotoxicity and changes in gene expression profiles influenced by commonly titanium (as titanium carbide, titanium carbo-nitride, titanium (II) oxide, titanium (III) oxide, titanium (IV) oxide, titanium nitride, titanium silicon oxide) NPs in human alveolar epithelial (HPAEpiC) and pharynx (HPPC) cell lines in vitro since inhalation is an important pathway for exposure to these nanoparticles...
December 28, 2016: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/27979969/noncanonical-wnt-5a-signaling-impairs-endogenous-lung-repair-in-copd
#20
Hoeke A Baarsma, Wioletta Skronska-Wasek, Kathrin Mutze, Florian Ciolek, Darcy E Wagner, Gerrit John-Schuster, Katharina Heinzelmann, Andreas Günther, Ken R Bracke, Maylis Dagouassat, Jorge Boczkowski, Guy G Brusselle, Ron Smits, Oliver Eickelberg, Ali Ö Yildirim, Melanie Königshoff
Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide. One main pathological feature of COPD is the loss of functional alveolar tissue without adequate repair (emphysema), yet the underlying mechanisms are poorly defined. Reduced WNT-β-catenin signaling is linked to impaired lung repair in COPD; however, the factors responsible for attenuating this pathway remain to be elucidated. Here, we identify a canonical to noncanonical WNT signaling shift contributing to COPD pathogenesis...
January 2017: Journal of Experimental Medicine
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