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Alveolar epithelial repair

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https://www.readbyqxmd.com/read/28193481/epigenetic-and-transcriptomic-regulation-of-lung-repair-during-recovery-from-influenza-infection
#1
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...
February 9, 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
#2
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
#3
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
#4
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
#5
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
#6
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...
January 6, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28044311/effects-of-hypercapnia-on-the-lung
#7
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...
January 3, 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
#8
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
#9
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
https://www.readbyqxmd.com/read/27957484/lipoxin-a4-promotes-lung-epithelial-repair-whilst-inhibiting-fibroblast-proliferation
#10
Shengxing Zheng, Vijay K D'Souza, Domokos Bartis, Rachel C A Dancer, Dhruv Parekh, Babu Naidu, Fang Gao-Smith, Qian Wang, Shengwei Jin, Qingquan Lian, David R Thickett
Therapy that promotes epithelial repair whilst protecting against fibroproliferation is critical for restoring lung function in acute and chronic respiratory diseases. Primary human alveolar type II cells were used to model the effects of lipoxin A4in vitro upon wound repair, proliferation, apoptosis and transdifferention. Effects of lipoxin A4 upon primary human lung fibroblast proliferation, collagen production, and myofibroblast differentiation were also assessed. Lipoxin A4 promoted type II cell wound repair and proliferation, blocked the negative effects of soluble Fas ligand/tumour necrosis factor α upon cell proliferation, viability and apoptosis, and augmented the epithelial cell proliferative response to bronchoaveolar lavage fluid (BALF) from acute respiratory distress syndrome (ARDS)...
July 2016: ERJ Open Research
https://www.readbyqxmd.com/read/27923370/the-cellular-kinetics-of-lung-alveolar-epithelial-cells-and-its-relationship-with-lung-tissue-repair-after-acute-lung-injury
#11
Ling Zeng, Xue-Tao Yang, Hai-Sheng Li, Yong Li, Ce Yang, Wei Gu, Yin-Han Zhou, Juan Du, Hai-Yan Wang, Jian-Hui Sun, Da-Lin Wen, Jian-Xin Jiang
BACKGROUND: Organ regeneration in mammals is hypothesized to require a functional pool of stem or progenitor cells, but the role of these cells in lung regeneration is unknown. METHODS: Based on the fact that postnatal regeneration of alveolar tissue has been attributed to alveolar epithelial cells, we established a hemorrhagic shock and Lipopolysaccharide (LPS) lung injury model. Using this model, we analyzed the cellular kinetics of lung alveolar epithelial cells...
December 7, 2016: Respiratory Research
https://www.readbyqxmd.com/read/27886850/cellular-senescence-and-autophagy-in-the-pathogenesis-of-chronic-obstructive-pulmonary-disease-copd-and-idiopathic-pulmonary-fibrosis-ipf
#12
REVIEW
Kazuyoshi Kuwano, Jun Araya, Hiromichi Hara, Shunsuke Minagawa, Naoki Takasaka, Saburo Ito, Kenji Kobayashi, Katsutoshi Nakayama
Aging is associated with impairments in homeostasis. Although aging and senescence are not equivalent, the number of senescent cells increases with aging. Cellular senescence plays important roles in tissue repair or remodeling, as well as embryonic development. Autophagy is a process of lysosomal self-degradation that maintains a homeostatic balance between the synthesis, degradation, and recycling of cellular proteins. Autophagy diminishes with aging; additionally, accelerated aging can be attributed to reduced autophagy...
November 2016: Respiratory Investigation
https://www.readbyqxmd.com/read/27861515/involvement-of-igf1r-in-bronchiolar-epithelial-regeneration-role-during-repair-kinetics-after-selective-club-cell-ablation
#13
Icíar P López, Sergio Piñeiro-Hermida, Rosete S Pais, Raquel Torrens, Andreas Hoeflich, José G Pichel
Regeneration of lung epithelium is vital for maintaining airway function and integrity. An imbalance between epithelial damage and repair is at the basis of numerous chronic lung diseases such as asthma, COPD, pulmonary fibrosis and lung cancer. IGF (Insulin-like Growth Factors) signaling has been associated with most of these respiratory pathologies, although their mechanisms of action in this tissue remain poorly understood. Expression profiles analyses of IGF system genes performed in mouse lung support their functional implication in pulmonary ontogeny...
2016: PloS One
https://www.readbyqxmd.com/read/27796509/lung-remodeling-associated-with-recovery-from-acute-lung-injury
#14
REVIEW
Sean E Gill, Cory M Yamashita, Ruud A W Veldhuizen
Acute respiratory distress syndrome (ARDS) is a disease with a variety of causes and is defined by severe hypoxemia. Whereas ARDS carries a mortality of approximately 30 %, patients that survive may ultimately regain near normal pulmonary physiology. The critical pathophysiological processes in ARDS are alveolar barrier dysfunction and overwhelming inflammation. This encompasses damage to the epithelial and endothelial layers, thickening of the interstitial matrix, edema with inactivation of pulmonary surfactant at the alveolar surface and marked inflammation mediated by infiltrating neutrophils and pro-inflammatory macrophages...
October 29, 2016: Cell and Tissue Research
https://www.readbyqxmd.com/read/27796199/establishing-proximal-and-distal-regional-identities-in-murine-and-human-tissue-engineered-lung-and-trachea
#15
Andrew Trecartin, Soula Danopoulos, Ryan Spurrier, Hanaa Knaneh-Monem, Michael Hiatt, Barbara Driscoll, Christian Hochstim, Denise Al-Alam, Tracy C Grikscheit
The cellular and molecular mechanisms that underpin regeneration of the human lung are unknown, and the study of lung repair has been impeded by the necessity for reductionist models that may exclude key components. We hypothesized that multicellular epithelial and mesenchymal cell clusters or lung organoid units (LuOU) could be transplanted to recapitulate proximal and distal cellular structures of the native lung and airways. Transplantation of LuOU resulted in the growth of tissue-engineered lung (TELu) that contained the necessary cell types consistent with native adult lung tissue and demonstrated proliferative cells at 2 and 4 weeks...
November 2016: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/27788331/cells-respond-to-distinct-nanoparticle-properties-with-multiple-strategies-as-revealed-by-single-cell-rna-seq
#16
Hugh D Mitchell, Lye Meng Markillie, William B Chrisler, Matthew J Gaffrey, Dehong Hu, Craig J Szymanski, Yumei Xie, Eric S Melby, Alice Dohnalkova, Ronald C Taylor, Eva K Grate, Scott K Cooley, Jason E McDermott, Alejandro Heredia-Langner, Galya Orr
The impact of distinct nanoparticle (NP) properties on cellular response and ultimately human health is unclear. This gap is partially due to experimental difficulties in achieving uniform NP loads in the studied cells, creating heterogeneous populations with some cells "overloaded" while other cells are loaded with few or no NPs. Yet gene expression studies have been conducted in the population as a whole, identifying generic responses, while missing unique responses due to signal averaging across many cells, each carrying different loads...
November 22, 2016: ACS Nano
https://www.readbyqxmd.com/read/27773701/rare-sox2-airway-progenitor-cells-generate-krt5-cells-that-repopulate-damaged-alveolar-parenchyma-following-influenza-virus-infection
#17
Samriddha Ray, Norika Chiba, Changfu Yao, Xiangrong Guan, Alicia M McConnell, Brian Brockway, Loretta Que, Jonathan L McQualter, Barry R Stripp
Recent studies have implicated keratin 5 (KRT5)(+) cells in repopulation of damaged lung tissue following severe H1N1 influenza virus infection. However, the origins of the cells repopulating the injured alveolar region remain controversial. We sought to determine the cellular dynamics of lung repair following influenza infection and define whether nascent KRT5(+) cells repopulating alveolar epithelium were derived from pre-existing alveolar or airway progenitor cells. We found that the wound-healing response begins with proliferation of SOX2(+) SCGB1A1(-) KRT5(-) progenitor cells in airways...
November 8, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27770432/fgf10-deficiency-is-causative-for-lethality-in-a-mouse-model-of-bronchopulmonary-dysplasia
#18
Cho-Ming Chao, Faady Yahya, Alena Moiseenko, Caterina Tiozzo, Amit Shrestha, Negah Ahmadvand, Elie El Agha, Jennifer Quantius, Salma Dilai, Vahid Kheirollahi, Matthew Jones, Jochen Wilhem, Gianni Carraro, Harald Ehrhardt, Klaus-Peter Zimmer, Guillermo Barreto, Katrin Ahlbrecht, Rory E Morty, Susanne Herold, Rosanna G Abellar, Werner Seeger, Ralph Schermuly, Jin-San Zhang, Parviz Minoo, Saverio Bellusci
Inflammation-induced FGF10 protein deficiency is associated with bronchopulmonary dysplasia (BPD), a chronic lung disease of prematurely born infants characterized by arrested alveolar development. So far, experimental evidence for a direct role of FGF10 in lung disease is lacking. Using the hyperoxia-induced neonatal lung injury as a mouse model of BPD, the impact of Fgf10 deficiency in Fgf10(+/-) versus Fgf10(+/+) pups was investigated. In normoxia, no lethality of Fgf10(+/+) or Fgf10(+/-) pups was observed...
January 2017: Journal of Pathology
https://www.readbyqxmd.com/read/27725837/dynamic-tracking-human-mesenchymal-stem-cells-tropism-following-smoke-inhalation-injury-in-nod-scid-mice
#19
MeiJuan Song, Qi Lv, XiuWei Zhang, Juan Cao, ShuLi Sun, PeiXin Xiao, ShiKe Hou, Hui Ding, ZiQuan Liu, WenLong Dong, JinQiang Wang, Xue Wang, ZhiGuang Sun, Man Tian, HaoJun Fan
Multiple preclinical evidences have supported the potential value of mesenchymal stem cells (MSCs) for treatment of acute lung injury (ALI). However, few studies focus on the dynamic tropism of MSCs in animals with acute lung injury. In this study, we track systemically transplanted human bone marrow-derived mesenchymal stem cells (hBMSCs) in NOD/SCID mice with smoke inhalation injury (SII) through bioluminescence imaging (BLI). The results showed that hBMSCs systemically delivered into healthy NOD/SCID mouse initially reside in the lungs and then partially translocate to the abdomen after 24 h...
2016: Stem Cells International
https://www.readbyqxmd.com/read/27694932/hyaluronan-and-tlr4-promote-surfactant-protein-c-positive-alveolar-progenitor-cell-renewal-and-prevent-severe-pulmonary-fibrosis-in-mice
#20
Jiurong Liang, Yanli Zhang, Ting Xie, Ningshan Liu, Huaiyong Chen, Yan Geng, Adrianne Kurkciyan, Jessica Monterrosa Mena, Barry R Stripp, Dianhua Jiang, Paul W Noble
Successful recovery from lung injury requires the repair and regeneration of alveolar epithelial cells to restore the integrity of gas-exchanging regions within the lung and preserve organ function. Improper regeneration of the alveolar epithelium is often associated with severe pulmonary fibrosis, the latter of which involves the recruitment and activation of fibroblasts, as well as matrix accumulation. Type 2 alveolar epithelial cells (AEC2s) are stem cells in the adult lung that contribute to the lung repair process...
November 2016: Nature Medicine
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