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Alveolar epithelial repair

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https://www.readbyqxmd.com/read/28662821/the-role-of-matrix-metalloproteinases-in-development-repair-and-destruction-of-the-lungs
#1
Amanda Y Hendrix, Farrah Kheradmand
Normal gas exchange after birth requires functional lung alveolar units that are lined with epithelial cells, parts of which are intricately fused with microvascular capillaries. A significant phase of alveolar lung development occurs in the perinatal period, continues throughout early stages in life, and requires activation of matrix-remodeling enzymes. Failure to achieve an optimum number of alveoli during lung maturation can cause several untoward medical consequences including disabling obstructive and/or restrictive lung diseases that limit physiological endurance and increase mortality...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/28657777/epithelial-deletion-of-sulf2-exacerbates-bleomycin-induced-lung-injury-inflammation-and-mortality
#2
Xinping Yue
Epithelial injury has been proposed to be the initiating factor in the pathogenesis of idiopathic pulmonary fibrosis (IPF). We have shown previously that heparan sulfate (HS) 6-O-endosulfatase 2 (Sulf2) is overexpressed in the hyperplastic type II alveolar epithelial cells (AECs) in the IPF lungs. By removing 6-O-sulfates from specific HS intra-chain sites, Sulf2 modulates the functions of many growth factors and cytokines. In this study we hypothesized that Sulf2 plays a regulatory role in alveolar epithelial injury and repair, using the murine bleomycin model...
June 28, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28637674/oxidative-stress-destabilizes-protein-arginine-methyltransferase-4-via-glycogen-synthase-kinase-3%C3%AE-to-impede-lung-epithelial-cell-migration
#3
Xiuying Li, Yandong Lai, Jin Li, Mingyi Zou, Chunbin Zou
Oxidative stress impacts normal cellular function leading to the pathogenesis of various diseases including pulmonary illnesses. Protein arginine methyltransferase 4 (PRMT4) is critical for normal lung alveolar epithelial cell development; however, the regulation of PRMT4 within such pulmonary diseases has yet to be elucidated. Using biochemical approaches, we uncovered that peroxide (H2O2) treatment decreases PRMT4 protein stability in murine lung epithelial (MLE12) cells to impede cell migration. Protein kinase glycogen synthase kinase 3β (GSK-3β) interacts with PRMT4 and catalyzes PRMT4 T132 phosphorylation that protects PRMT4 from ubiquitin proteasomal degradation...
June 21, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28618253/hypoxia-inducible-factor-1%C3%AE-signaling-promotes-repair-of-the-alveolar-epithelium-after-acute-lung-injury
#4
Jazalle McClendon, Nicole L Jansing, Elizabeth F Redente, Aneta Gandjeva, Yoko Ito, Sean P Colgan, Aftab Ahmad, David W H Riches, Harold A Chapman, Robert J Mason, Rubin M Tuder, Rachel L Zemans
During acute respiratory distress syndrome, epithelial cells, primarily alveolar type (AT) I cells, die and slough off the basement membrane, resulting in enhanced permeability. ATII cells proliferate and spread onto the denuded basement membrane to reseal the barrier. Repair of the alveolar epithelium is critical for clinical recovery; however, the mechanisms underlying ATII cell proliferation and spreading are not well understood. We hypothesized that hypoxia-inducible factor (HIF)1α promotes proliferation and spreading of ATII cells during repair after lung injury...
June 12, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28615712/cell-specific-expression-of-aquaporin-5-aqp5-in-alveolar-epithelium-is-directed-by-gata6-sp1-via-histone-acetylation
#5
Per Flodby, Changgong Li, Yixin Liu, Hongjun Wang, Megan E Rieger, Parviz Minoo, Edward D Crandall, David K Ann, Zea Borok, Beiyun Zhou
Epigenetic regulation of differentiation-related genes is poorly understood. We previously reported that transcription factors GATA6 and Sp1 interact with and activate the rat proximal 358-bp promoter/enhancer (p358P/E) of lung alveolar epithelial type I (AT1) cell-specific gene aquaporin-5 (Aqp5). In this study, we found that histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) increased AQP5 expression and Sp1-mediated transcription of p358P/E. HDAC3 overexpression inhibited Sp1-mediated Aqp5 activation, while HDAC3 knockdown augmented AQP5 protein expression...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28593053/natural-graft-tissues-and-synthetic-biomaterials-for-periodontal-and-alveolar-bone-reconstructive-applications-a-review
#6
REVIEW
Zeeshan Sheikh, Nader Hamdan, Yuichi Ikeda, Marc Grynpas, Bernhard Ganss, Michael Glogauer
Periodontal disease is categorized by the destruction of periodontal tissues. Over the years, there have been several clinical techniques and material options that been investigated for periodontal defect repair/regeneration. The development of improved biomaterials for periodontal tissue engineering has significantly improved the available treatment options and their clinical results. Bone replacement graft materials, barrier membranes, various growth factors and combination of these have been used. The available bone tissue replacement materials commonly used include autografts, allografts, xenografts and alloplasts...
2017: Biomaterials Research
https://www.readbyqxmd.com/read/28587419/regulation-of-the-angiotensin-ii-p22phox-reactive-oxygen-species-signaling-pathway-apoptosis-and-8-oxoguanine-dna-glycosylase-1-retrieval-in-hyperoxia-induced-lung-injury-and-fibrosis-in-rats
#7
Yu Wang, Yuxi Zhu, Yudi Zhu, Zhongyi Lu, Feng Xu
The present study was designed to explore the impact of hyperoxia on lung injury and fibrosis via the angiotensin II (AngII)-p22phox-reactive oxygen species (ROS) signaling pathway, apoptosis and 8-oxoguanine-DNA glycosylase 1 (OGG1) repair enzyme. Newborn Sprague-Dawley rats were randomly divided in the newborn air group, newborn hyperoxia group and newborn intervention group, the latter of which was administered the chymotrypsin inhibitor, 2-(5-formylamino-6-oxo-2-phenyl-1, 6-dihydropyrimidine-1-yl)-N-[4-dioxo-1-phenyl-7-(2-pyridyloxy)] 2-heptyl-acetamide (NK3201)...
June 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28586241/unbiased-quantitation-of-atii-to-ati-cell-transdifferentiation-during-repair-after-lung-injury-in-mice
#8
Nicole L Jansing, Jazalle McClendon, Peter M Henson, Rubin M Tuder, Dallas M Hyde, Rachel L Zemans
The alveolar epithelium consists of squamous alveolar type (AT)I and cuboidal ATII cells. ATI cells cover 95-98% of the alveolar surface, thereby playing a critical role in barrier integrity, and are extremely thin, thus permitting efficient gas exchange. During lung injury, ATI cells die, resulting in increased epithelial permeability. ATII cells reepithelialize the alveolar surface via proliferation and transdifferentiation into ATI cells. Transdifferentiation is characterized by downregulation of ATII cell markers, upregulation of ATI cell markers, and cell spreading resulting in a change in morphology from cuboidal to squamous, thus restoring normal alveolar architecture and function...
June 6, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28526890/a-heteromeric-molecular-complex-regulates-the-migration-of-lung-alveolar-epithelial-cells-during-wound-healing
#9
Manik C Ghosh, Patrudu S Makena, Joseph Kennedy, Bin Teng, Charlean Luellen, Scott E Sinclair, Christopher M Waters
Alveolar type II epithelial cells (ATII) are instrumental in early wound healing in response to lung injury, restoring epithelial integrity through spreading and migration. We previously reported in separate studies that focal adhesion kinase-1 (FAK) and the chemokine receptor CXCR4 promote epithelial repair mechanisms. However, potential interactions between these two pathways were not previously considered. In the present study, we found that wounding of rat ATII cells promoted increased association between FAK and CXCR4...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428174/klotho-an-antiaging-molecule-attenuates-oxidant-induced-alveolar-epithelial-cell-mtdna-damage-and-apoptosis
#10
Seok-Jo Kim, Paul Cheresh, Mesut Eren, Renea P Jablonski, Anjana Yeldandi, Karen M Ridge, G R Scott Budinger, Dong-Hyun Kim, Myles Wolf, Douglas E 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 antiaging 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...
July 1, 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
#11
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
#12
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
#13
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
#14
Qiang Ding, Indhu Subramanian, Tracy R Luckhardt, Pulin Che, Meghna Waghray, Xue-Ke Zhao, Nathaniel Bone, Ashish R Kurundkar, Louise Hecker, Meng Hu, Yong Zhou, Jeffrey C 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 response 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 transforming growth factor-β1 (TGF-β1). Rat type II alveolar epithelial cells (RLE-6TN) were treated with or without TGF-β1, and the expressions of mesenchymal markers, phenotype, and function were analyzed...
June 1, 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
#15
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
#16
REVIEW
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
#17
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
#18
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-chronic-obstructive-pulmonary-disease
#19
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. Wingless and INT-1 (WNT)/β-catenin signaling is reduced in COPD; however, the mechanisms thereof, specifically the role of the frizzled (FZD) family of WNT receptors, remain unexplored. OBJECTIVES: To identify and functionally characterize specific FZD receptors that control downstream WNT signaling in impaired lung repair in COPD...
July 15, 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
#20
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
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