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Alveolar epithelial repair

Valérie Besnard, Rania Dagher, Tania Madjer, Audrey Joannes, Madeleine Jaillet, Martin Kolb, Philippe Bonniaud, Lynne A Murray, Matthew A Sleeman, Bruno Crestani
Periplakin is a component of the desmosomes that acts as a cytolinker between intermediate filament scaffolding and the desmosomal plaque. Periplakin is strongly expressed by epithelial cells in the lung and is a target antigen for autoimmunity in idiopathic pulmonary fibrosis. The aim of this study was to determine the role of periplakin during lung injury and remodeling in a mouse model of lung fibrosis induced by bleomycin. We found that periplakin expression was downregulated in the whole lung and in alveolar epithelial cells following bleomycin-induced injury...
March 8, 2018: JCI Insight
Michael F Nyp, Sherry M Mabry, Angels Navarro, Heather Menden, Ricardo E Perez, Venkatesh Sampath, Ikechukwu I Ekekezie
The onset and degree of injury occurring in animals that develop hyperoxic acute lung injury (HALI) is dependent on age at exposure, suggesting that developmentally regulated pathways/factors must underlie initiation of the epithelial injury and subsequent repair. Type II TGFβ receptor interacting protein-1 (TRIP-1) is a negative regulator of TGFβ signaling, which we have previously shown is a developmentally regulated protein with modulatory effects on epithelial-fibroblastic signaling. The aim of this study was to assess if type II alveolar epithelial cells overexpressing TRIP-1 are protected against hyperoxia-induced epithelial injury, and in turn HALI...
March 2018: Physiological Reports
Giacomo Sgalla, Bruno Iovene, Mariarosaria Calvello, Margherita Ori, Francesco Varone, Luca Richeldi
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive disease characterized by the aberrant accumulation of fibrotic tissue in the lungs parenchyma, associated with significant morbidity and poor prognosis. This review will present the substantial advances achieved in the understanding of IPF pathogenesis and in the therapeutic options that can be offered to patients, and will address the issues regarding diagnosis and management that are still open. MAIN BODY: Over the last two decades much has been clarified about the pathogenic pathways underlying the development and progression of the lung scarring in IPF...
February 22, 2018: Respiratory Research
Li-Yin Hung, Taylor K Oniskey, Debasish Sen, Matthew F Krummel, Andrew E Vaughan, Noam A Cohen, De'Broski R Herbert
Trefoil factors are small secreted proteins that regulate tissue integrity and repair at mucosal surfaces, particularly in the gastrointestinal tract. However, their relative contribution(s) to controlling baseline lung function or the extent of infection-induced lung injury are unknown issues. Using irradiation bone marrow chimeras, we found that Trefoil factor 2 (TFF2) produced from both hematopoietic- and non-hematopoietic-derived cells is essential for host protection, proliferation of alveolar type 2 cells, and restoration of pulmonary gas exchange following infection with the hookworm parasite Nippostrongylus brasiliensis...
February 16, 2018: American Journal of Pathology
Jinfeng Liu, Wei Wang, Fengli Liu, Zhenguang Li
Acute respiratory distress syndrome (ARDS) mainly involves acute respiratory failure. In addition to this affected patients feel progressive arterial hypoxemia, dyspnea, and a marked increase in the work of breathing. The only clinical solution for the above pathological state is ventilation. Mechanical ventilation is necessary to support life in ARDs but it itself worsen lung injury and the term is known clinically as 'ventilation induced lung injury' (VILI). At the cellular level, respiratory epithelial cells are subjected to cyclic stretch, i...
February 2018: Experimental and Therapeutic Medicine
Reiko Sakurai, Cindy Lee, Humphrey Shen, Alan J Waring, Frans J Walther, Virender K Rehan
BACKGROUND: Despite improvements in perinatal care, bronchopulmonary dysplasia (BPD) in extremely premature infants has not decreased. Postnatal surfactant therapy provides symptomatic relief from respiratory distress syndrome, but does not translate into a reduction in BPD. Therefore, the search for effective interventions to prevent BPD continues. OBJECTIVES: Since PPAR-γ agonists have been demonstrated to promote neonatal lung maturation and injury repair, we hypothesized that a formulation of a PPAR-γ agonist, pioglitazone (PGZ) and a synthetic lung surfactant (a surfactant protein B peptide mimic, B-YL) combined would stimulate lung maturation and block hyperoxia-induced neonatal lung injury more effectively than either modality alone...
February 9, 2018: Neonatology
Beiyun Zhou, Per Flodby, Jiao Luo, Dan R Castillo, Yixin Liu, Fa-Xing Yu, Alicia McConnell, Bino Varghese, Guanglei Li, Nyam-Osor Chimge, Mitsuhiro Sunohara, Michael N Koss, Wafaa Elatre, Peter Conti, Janice M Liebler, Chenchen Yang, Crystal N Marconett, Ite A Laird-Offringa, Parviz Minoo, Kunliang Guan, Barry R Stripp, Edward D Crandall, Zea Borok
Claudins, the integral tight junction (TJ) proteins that regulate paracellular permeability and cell polarity, are frequently dysregulated in cancer; however, their role in neoplastic progression is unclear. Here, we demonstrated that knockout of Cldn18, a claudin family member highly expressed in lung alveolar epithelium, leads to lung enlargement, parenchymal expansion, increased abundance and proliferation of known distal lung progenitors, the alveolar epithelial type II (AT2) cells, activation of Yes-associated protein (YAP), increased organ size, and tumorigenesis in mice...
February 5, 2018: Journal of Clinical Investigation
Tiankai Xu, Yuyu Zhang, Pengyu Chang, Shouliang Gong, Lihong Shao, Lihua Dong
Since radiotherapy is widely used in managing thoracic tumors, physicians have begun to realize that radiation-induced lung injury (RILI) seriously limits the effects of radiotherapy. Unfortunately, there are still no effective methods for controlling RILI. Over the last few decades numerous studies have reported the beneficial effects of mesenchymal stem cells (MSCs) on tissue repair and regeneration. MSCs can not only differentiate into lung alveolar epithelial cells and secrete anti-inflammatory factors, but they also deliver some vehicles for gene therapy in repairing the injured lung, which provides new ideas for managing RILI...
January 31, 2018: Stem Cell Research & Therapy
Sofie Van Den Broucke, Lore Pollaris, Greetje Vande Velde, Erik Verbeken, Benoit Nemery, Jeroen Vanoirbeek, Peter Hoet
Inhalation of commonly present irritants, such as chlorine and chlorine derivatives, can cause adverse respiratory effects, including irritant-induced asthma (IIA). We hypothesize that due to airway barrier impairment, exposure to hypochlorite (ClO-) can result in airway hypersensitivity. C57Bl/6 mice received an intra-peritoneal (i.p.) injection of the airway damaging agent naphthalene (NA, 200 mg/kg body weight) or vehicle (mineral oil, MO). In vivo micro-computed tomography (CT) images of the lungs were acquired before and at regular time points after the i...
January 24, 2018: Archives of Toxicology
Chloé Michaudel, Claire Mackowiak, Isabelle Maillet, Louis Fauconnier, Cezmi Akdis, Milena Sokolowska, Anita Dreher, Hern-Tze Tina Tan, Valérie F Quesniaux, Bernhard Ryffel, Dieudonnée Togbe
BACKGROUND: IL-33 plays critical role in the regulation of tissue homeostasis, injury and repair. Whether IL-33 regulates neutrophil recruitment and function independently of airways hyperresponsiveness (AHR) in ozone induced lung injury and inflammation is unclear. OBJECTIVE: To examine the role of IL-33/ST2 axis in lung inflammation upon acute ozone exposure in mice. METHODS: ST2 and IL-33 deficient mice, IL-33-citrine reporter and C57BL/6 (WT) mice underwent a single ozone exposure (1 ppm for 1h) in all studies...
January 10, 2018: Journal of Allergy and Clinical Immunology
Barbara Rindlisbacher, Cornelia Schmid, Thomas Geiser, Cédric Bovet, Manuela Funke-Chambour
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease of unknown etiology. Patients present loss of lung function, dyspnea and dry cough. Diagnosis requires compatible radiologic imaging and, in undetermined cases, invasive procedures such as bronchoscopy and surgical lung biopsy. The pathophysiological mechanisms of IPF are not completely understood. Lung injury with abnormal alveolar epithelial repair is thought to be a major cause for activation of profibrotic pathways in IPF...
January 10, 2018: Respiratory Research
Raquel Guillamat-Prats, Ferranda Puig, Marta Camprubí-Rimblas, Raquel Herrero, Anna Serrano-Mollar, Maria Nieves Gómez, Jessica Tijero, Michael A Matthay, Lluís Blanch, Antonio Artigas
BACKGROUND: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are characterized by excess production of inflammatory factors. Alveolar type II (ATII) cells help repair damaged lung tissue, rapidly proliferating and differentiating into alveolar type I cells after epithelial cell injury. In ALI, the lack of viable ATII favors progression to more severe lung injury. ATII cells regulate the immune response by synthesizing surfactant and other anti-inflammatory proteins and lipids...
November 8, 2017: Journal of Heart and Lung Transplantation
Yu-Xin Bai, Fang Fang, Jia-Ling Jiang, Feng Xu
BACKGROUND Lung alveolar epithelial type II cells (AEC II) are the most important stem cells in lung tissues, which are critical for wound repair of bronchopulmonary dysplasia (BPD). This study investigated the effects of calcitonin gene-related peptide (CGRP) on AEC II cells exposed to hyperoxia. MATERIAL AND METHODS Neonatal rat AEC II cells were isolated and identified by detecting surfactant protein C (SP-C). Three small interfering RNAs targeting Notch 1 were synthesized and transfected into AEC II. A hyperoxia-exposed AEC II cell injury model was established and was divided into 8 groups...
December 5, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Keyu Wang, Chengcai Lai, Hongjing Gu, Lingna Zhao, Min Xia, Penghui Yang, Xiliang Wang
Fibroblast growth factor 2 (FGF2 or basic FGF) regulates a wide range of cell biological functions including proliferation, angiogenesis, migration, differentiation, and injury repair. However, the roles of FGF2 and the underlying mechanisms of action in influenza A virus (IAV)-induced lung injury remain largely unexplored. In this study, we report that microRNA-194-5p (miR-194) expression is significantly decreased in A549 alveolar epithelial cells (AECs) following infection with IAV/Beijing/501/2009 (BJ501)...
2017: Frontiers in Microbiology
Catherine R Sears, Huaxin Zhou, Matthew J Justice, Amanda J Fisher, Jacob Saliba, Isaac Lamb, Jessica Wicker, Kelly S Schweitzer, Irina Petrache
Cigarette smoke (CS) exposure is a major risk factor for the development of emphysema, a common disease characterized by loss of cells comprising the lung parenchyma. The mechanisms of cell injury leading to emphysema are not completely understood but are thought to involve persistent cytotoxic or mutagenic DNA damage induced by CS. Using complementary cell culture and mouse models of CS exposure, we investigated the role of the DNA repair protein xeroderma pigmentosum group C (XPC) on CS-induced DNA damage repair and emphysema...
November 7, 2017: American Journal of Respiratory Cell and Molecular Biology
Shengxing Zheng, Qian Wang, Vijay D'Souza, Dom Bartis, Rachel Dancer, Dhruv Parekh, Fang Gao, Qingquan Lian, Shengwei Jin, David R Thickett
Acute and chronic inflammatory lung diseases are often associated with epithelial cell injury/loss and fibroproliferative responses. ResolvinD1 (RvD1) is biosynthesized during the resolution phase of inflammatory response and exerts potent anti-inflammatory and promotes resolution of inflammatory lung diseases. The aim of this study was to investigate whether RvD1 exerts protective effects on alveolar epithelial cell function/differentiation and protects against fibroproliferative stimuli. Primary human alveolar type II cells were used to model the effects of RvD1 in vitro upon wound repair, proliferation, apoptosis, transdifferentiation, and epithelial-mesenchymal transition (EMT)...
October 30, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
Mehdi Shafa, Lavinia Iuliana Ionescu, Arul Vadivel, Jennifer J P Collins, Liqun Xu, Shumei Zhong, Martin Kang, Geneviève de Caen, Manijeh Daneshmand, Jenny Shi, Katherine Z Fu, Andrew Qi, Ying Wang, James Ellis, William L Stanford, Bernard Thébaud
BACKGROUND AIMS: Bronchopulmonary dysplasia (BPD), a chronic lung disease characterized by disrupted lung growth, is the most common complication in extreme premature infants. BPD leads to persistent pulmonary disease later in life. Alveolar epithelial type 2 cells (AEC2s), a subset of which represent distal lung progenitor cells (LPCs), promote normal lung growth and repair. AEC2 depletion may contribute to persistent lung injury in BPD. We hypothesized that induced pluripotent stem cell (iPSC)-derived AECs prevent lung damage in experimental oxygen-induced BPD...
October 20, 2017: Cytotherapy
Yang Li, Xiaojie Chu, Cunbao Liu, Weiwei Huang, Yufeng Yao, Ye Xia, Pengyan Sun, Qiong Long, Xuejun Feng, Kui Li, Xu Yang, Hongmei Bai, Wenjia Sun, Yanbing Ma
Cathelicidin has been reported to be multifunctional. The current study aimed to investigate the influences of exogenous cathelicidin-related antimicrobial peptide (CRAMP) on inflammatory responses in different disease models. In OVA-induced allergic airway inflammation, CRAMP significantly enhanced the infiltration of inflammatory cells and accumulation of proinflammatory Th2 cytokine IL-13 and IL-33 in bronchial alveolar lavage fluid (BALF), exacerbated lung tissue inflammation and airway goblet cell hyperplasia, and elevated OVA-specific IgE level in serum...
January 2, 2018: Human Vaccines & Immunotherapeutics
Michael Kasper, Kathrin Barth
Pulmonary fibrosis (PF) is characterized by inflammation and fibrosis of the interstitium and destruction of alveolar histoarchitecture ultimately leading to a fatal impairment of lung function. Different concepts describe either a dominant role of inflammatory pathways or a disturbed remodeling of resident cells of the lung parenchyma during fibrogenesis. Further, a combination of both the mechanisms has been postulated. The present review emphasizes the particular involvement of alveolar epithelial type I cells in all these processes, their contribution to innate immune/inflammatory functions and maintenance of proper alveolar barrier functions...
December 22, 2017: Bioscience Reports
Wen-Ya Li, Xu-Lv Ye, Xin-Shan Jia, Lan-Ling Jia
OBJECTIVE: We aimed to investigate how the embryonic stem cell-related gene Oct3/4 changes during the injury-repair process of distal pulmonary epithelium induced by 5-fluorouracil (5-Fu). METHODS: We have developed the lung injury model induced by 5-Fu and observed the dynamic changes of Oct3/4 by indirect immunofluorescence, Western blot, and quantitative real-time PCR. Immunofluorescence double staining was used to compare the positions of Oct3/4(+) cells and other reported alveolar epithelial stem cells...
2017: BioMed Research International
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