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Alveolar epithelial injury

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https://www.readbyqxmd.com/read/28314802/an-ex-vivo-model-to-induce-early-fibrosis-like-changes-in-human-precision-cut-lung-slices
#1
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
#2
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/28283477/lung-epithelial-cell-focal-adhesion-kinase-signaling-inhibits-lung-injury-and-fibrosis
#3
Amanda K Wheaton, Manisha Agarwal, Shijing Jia, Kevin K Kim
Progressive pulmonary fibrosis is a devastating consequence of many acute and chronic insults to the lung. Lung injury leads to alveolar epithelial cell (AEC) death, destruction of the basement membrane and activation of TGFβ. There is subsequent resolution of the injury and a coordinated and concurrent initiation of fibrosis. Both of these processes may involve activation of similar intracellular signaling pathways regulated in part by dynamic changes to the extracellular matrix. Matrix signaling can augment the pro-fibrotic fibroblast response to TGFβ...
March 10, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28273432/p53-and-mir-34a-feedback-promotes-lung-epithelial-injury-and-pulmonary-fibrosis
#4
Shwetha K Shetty, Nivedita Tiwari, Amarnath S Marudamuthu, Bijesh Puthusseri, Yashodhar P Bhandary, Jian Fu, Jeffrey Levin, Steven Idell, Sreerama Shetty
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease. The pathogenesis of interstitial lung diseases, including its most common form, IPF, remains poorly understood. Alveolar epithelial cell (AEC) apoptosis, proliferation, and accumulation of myofibroblasts and extracellular matrix deposition results in progressive loss of lung function in IPF. We found induction of tumor suppressor protein, p53, and apoptosis with suppression of urokinase-type plasminogen activator (uPA) and the uPA receptor in AECs from the lungs of IPF patients, and in mice with bleomycin, cigarette smoke, silica, or sepsis-induced lung injury...
March 5, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28247763/n-n-dimethyl-tertiary-amino-group-mediated-dual-pancreas-and-lung-targeting-therapy-against-acute-pancreatitis
#5
Shi Luo, Peiwen Li, Sha Li, Zhengwu Du, Xun Hu, Yao Fu, Zhirong Zhang
Acute pancreatitis (AP) is a sudden inflammation of the pancreas with high-mortality rate worldwide. As a severe complication to AP, acute lung injury has been the major cause of death among patients with AP. Poor penetration across the blood pancreas barrier (BPB), and insufficient drug accumulation at the target site often result in poor therapeutic outcome. Our previous work successfully demonstrated a dual-specific targeting strategy to pancreas and lung using a phenolic propanediamine moiety. Inspired by this, a simplified ligand structure, N, N-dimethyl tertiary amino group, was covalently conjugated to celastrol (CLT) to afford tertiary amino conjugates via either an ester (CP) or an amide linkage (CTA)...
March 1, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28245985/4-pba-inhibits-lps-induced-inflammation-through-regulating-er-stress-and-autophagy-in-acute-lung-injury-models
#6
Meichun Zeng, Wenhua Sang, Sha Chen, Ran Chen, Hailin Zhang, Feng Xue, Zhengmao Li, Yu Liu, Yongsheng Gong, Hongyu Zhang, Xiaoxia Kong
Acute lung injury (ALI) is a common clinical disorder that causes substantial health problems worldwide. An excessive inflammatory response is the central feature of ALI, but the mechanism is still unclear, especially the role of endoplasmic-reticulum (ER) stress and autophagy. To identify the cellular mechanism of lung inflammation during lipopolysaccharide (LPS)-induced mouse model of ALI, we investigated the influence of classic ER stress inhibitor 4-phenyl butyric acid (4-PBA) on ER stress and autophagy, which partially affect the activation of inflammation, both in LPS-induced ALI mouse model and human alveolar epithelial cell model...
February 27, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28228225/-advances-in-classification-and-research-methods-of-lung-epithelial-stem-%C3%A2-and-progenitor-cells
#7
Minhua Deng, Jinhua Li, Ye Gan, Ping Chen
Isolation and characterization of lung epithelial stem and progenitor cells and understanding of their specific role in lung physiopathology are critical for preventing and controlling lung diseases including lung cancer. In this review, we summarized recent advances in classification and research methods of lung epithelial stem and progenitor cells. Lung epithelial stem and progenitor cells were region-specific, which primarily included basal cells and duct cells in proximal airway, Clara cells, variant Clara cells, bronchioalveolar stem cells and induced krt5+ cells in bronchioles, type II alveolar cells and type II alveolar progenitor cells in alveoli...
February 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28218740/maresin1-stimulates-alveolar-fluid-clearance-through-the-alveolar-epithelial-sodium-channel-na-k-atpase-via-the-alx-pi3k-nedd4-2-pathway
#8
Jun-Li Zhang, Xiao-Jun Zhuo, Jing Lin, Ling-Chun Luo, Wei-Yang Ying, Xiang Xie, Hua-Wei Zhang, Jing-Xiang Yang, Dan Li, Fang Gao Smith, Sheng-Wei Jin
Maresin1 (MaR1) is a new docosahexaenoic acid-derived pro-resolving agent that promotes the resolution of inflammation. In this study, we sought to investigate the effect and underlining mechanisms of MaR1 in modulating alveolar fluid clearance (AFC) on LPS-induced acute lung injury. MaR1 was injected intravenously or administered by instillation (200 ng/kg) 8 h after LPS (14 mg/kg) administration and AFC was measured in live rats. In primary rat alveolar type II epithelial cells, MaR1 (100 nM) was added to the culture medium with lipopolysaccharide for 6 h...
February 20, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28213470/higher-mini-bal-total-protein-concentration-in-early-ards-predicts-faster-resolution-of-lung-injury-measured-by-more-ventilator-free-days
#9
Carolyn M Hendrickson, Jason Abbott, Hanjing Zhuo, Kathleen D Liu, Carolyn S Calfee, Michael A Matthay
The protein concentration of alveolar edema fluid in acute respiratory distress syndrome (ARDS) is dynamic. It reflects alveolar flooding during acute injury as well as fluid and protein clearance over time. We hypothesized that among ARDS patients treated with low tidal volume ventilation, higher concentrations of protein in mini-bronchoalveolar lavage (mBAL) samples would predict slower resolution of lung injury and worse clinical outcomes. Total protein and IgM concentrations in Day 0 mBAL samples from 79 subjects enrolled in the aerosolized albuterol (ALTA) ARDS Network Albuterol trial were measured by colorimetric assay and ELISA respectively...
February 17, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28212617/surfactant-protein-d-sp-d-gene-polymorphisms-and-serum-level-as-predictors-of-susceptibility-and-prognosis-of-acute-kidney-injury-in-the-chinese-population
#10
Jiao Liu, Guang Li, Lianghai Li, Zhiyong Liu, Qingshan Zhou, Guirong Wang, Dechang Chen
BACKGROUND: Injury to the kidney epithelial barrier is a characteristic feature of acute kidney injury (AKI). Serum surfactant protein-D (SP-D), a known biomarker of damaged alveolar epithelium, is also secreted by renal tubular epithelial cells. Therefore, the aim of this study was to examine the possible association of SP-D with AKI susceptibility and prognosis. METHODS: In this study, 159 AKI patients and 120 healthy individuals were included. SP-D polymorphisms Thr11Met and Thr160Ala, AKI patient serum SP-D levels at days 1, 3 and 7 and urine KIM-1 levels in both AKI patients and controls were examined...
February 17, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28196122/detrimental-elavl-1-hur-dependent-gsk3%C3%AE-mrna-stabilization-impairs-resolution-in-acute-respiratory-distress-syndrome
#11
Olivia Hoffman, Nana Burns, István Vadász, Holger K Eltzschig, Michael G Edwards, Christine U Vohwinkel
A hallmark of acute respiratory distress syndrome (ARDS) is accumulation of protein-rich edema in the distal airspaces and its removal is critical for patient survival. Previous studies have shown a detrimental role of Glycogen Synthase Kinase (GSK) 3β during ARDS via inhibition of alveolar epithelial protein transport. We hypothesized that post-transcriptional regulation of GSK3β could play a functional role in ARDS resolution. To address this hypothesis, we performed an in silico analysis to identify regulatory genes whose expression correlation to GSK3β messenger RNA utilizing two lung cancer cell line array datasets...
2017: PloS One
https://www.readbyqxmd.com/read/28195073/effects-of-budesonide-on-the-lung-functions-inflammation-and-apoptosis-in-a-saline-lavage-model-of-acute-lung-injury
#12
D Mokra, P Kosutova, S Balentova, M Adamkov, P Mikolka, J Mokry, M Antosova, A Calkovska
Diffuse alveolar injury, edema, and inflammation are fundamental signs of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Whereas the systemic administration of corticosteroids previously led to controversial results, this study evaluated if corticosteroids given intratracheally may improve lung functions and reduce edema formation, migration of cells into the lung and their activation in experimentally-induced ALI. In oxygen-ventilated rabbits, ALI was induced by repetitive saline lung lavage, until PaO2 decreased to < 26...
December 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28186665/dexmedetomidine-enhances-human-lung-fluid-clearance-through-improving-alveolar-sodium-transport
#13
Yong Cui, Yan Ding, Lei Chen, Yue Li, Yan Chun Li, Hongguang Nie
Accumulating evidence shows that dexmedetomidine can attenuate lung edema with acute lung injury in experimental mouse and rat models, but the mechanisms of dexmedetomidine on human alveolar fluid transport are still unknown. We measured the effects of dexmedetomidine on alveolar fluid clearance in human lung lobes ex vivo. Moreover, we measured the regulation of transepithelial Na(+) transport by dexmedetomidine in H441 cells by electrophysiological technique and western blot method. Our results showed that intratracheal instillation of dexmedetomidine markedly increased the re-absorption of 5% bovine serum albumin instillate (19...
February 10, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28161733/1%C3%AE-25-dihydroxyvitamin-d3-ameliorates-seawater-aspiration-induced-lung-injury-by-inhibiting-the-translocation-of-nf-%C3%AE%C2%BAb-and-rhoa
#14
Minlong Zhang, Faguang Jin
Our previous study have reported that 1α,25-Dihydroxyvitamin D3 (calcitriol) suppresses seawater aspiration-induced ALI in vitro and in vivo. We also have confirmed that treatment with calcitriol ameliorates seawater aspiration-induced inflammation and pulmonary edema via the inhibition of NF-κB and RhoA/Rho kinase pathway activation. In our further work, we investigated the effect of calcitriol on nuclear translocation of NF-κB and membrane translocation of RhoA in vitro. A549 cells and rat pulmonary microvascular endothelial cells (RPMVECs) were cultured with calcitriol or not for 48 h and then stimulated with 25% seawater for 40 min...
February 4, 2017: Inflammation
https://www.readbyqxmd.com/read/28151947/lung-protection-by-inhalation-of-exogenous-solubilized-extracellular-matrix
#15
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/28137591/amphiregulin-suppresses-epithelial-cell-apoptosis-in-lipopolysaccharide-induced-lung-injury-in-mice
#16
Saiko Ogata-Suetsugu, Toyoshi Yanagihara, Naoki Hamada, Chika Ikeda-Harada, Tetsuya Yokoyama, Kunihiro Suzuki, Tomonobu Kawaguchi, Takashige Maeyama, Kazuyoshi Kuwano, Yoichi Nakanishi
BACKGROUND AND OBJECTIVE: As a member of the epidermal growth factor family, amphiregulin contributes to the regulation of cell proliferation. Amphiregulin was reported to be upregulated in damaged lung tissues in patients with chronic obstructive pulmonary disease and asthma and in lung epithelial cells in a ventilator-associated lung injury model. In this study, we investigated the effect of amphiregulin on lipopolysaccharide (LPS)-induced acute lung injury in mice. METHODS: Acute lung injury was induced by intranasal instillation of LPS in female C57BL/6 mice, and the mice were given intraperitoneal injections of recombinant amphiregulin or phosphate-buffered saline 6 and 0...
January 28, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28080141/low-concentration-of-oleic-acid-exacerbates-lps-induced-cell-death-and-inflammation-in-human-alveolar-epithelial-cells
#17
Altug Kucukgul, Suat Erdogan
PURPOSE: The current study aimed to investigate in vitro effects of oleic acid on lipopolysaccharide (LPS)-induced acute lung injury in the human lung epithelial cells (A549). MATERIALS AND METHODS: The cell viability was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) tests. Selected gene expression levels were analyzed by Real-Time Quantitative-Polymerase Chain Reaction (RT-qPCR). RESULTS: 24 hours of LPS (100 ng/mL) exposure decreased the cells viability by 44...
January 12, 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/28077319/role-of-insulin-like-growth-factor-axis-in-the-bleomycin-induced-lung-injury-in-rats
#18
Lakshmi Kanth Kotarkonda, Ritu Kulshrestha, Krishnan Ravi
BACKGROUND: Alveolar epithelial cell injury has been proposed as a causative factor for the onset and progression of pulmonary fibrosis. However, the role of type II alveolar epithelial cells (AECs) in the epithelial mesenchymal transition (EMT) is controversial. AIMS: The present study performed in rats instilled with bleomycin investigated a) the expressions of the insulin growth factor (IGF-1) and insulin growth factor binding protein 5 (IGFBP-5) and transforming growth factor (TGF-β1) in the type II AECs, b) the role of type II AECs in EMT and extracellular matrix (ECM) formation and, c) the effect of pioglitazone on all the above parameters...
January 7, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28077237/interplay-of-extracellular-matrix-and-leukocytes-in-lung-inflammation
#19
REVIEW
Thomas N Wight, Charles W Frevert, Jason S Debley, Stephen R Reeves, William C Parks, Steven F Ziegler
During inflammation, leukocytes influx into lung compartments and interact with extracellular matrix (ECM). Two ECM components, versican and hyaluronan, increase in a range of lung diseases. The interaction of leukocytes with these ECM components controls leukocyte retention and accumulation, proliferation, migration, differentiation, and activation as part of the inflammatory phase of lung disease. In addition, bronchial epithelial cells from asthmatic children co-cultured with human lung fibroblasts generate an ECM that is adherent for monocytes/macrophages...
February 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28076504/the-role-of-bradykinin-in-lung-ischemia-reperfusion-injury-in-a-rat-lung-transplantation-model
#20
Zheng Tang, Zhiwei Wang, Zhipeng Hu, Min Zhang, Luocheng Li, Bowen Li
PURPOSE: To investigate the role of bradykinin in a rat lung transplantation (LTx) model and preliminarily discuss the relationship between bradykinin and CD26/DPP-4. METHODS: Rats were randomly divided into four groups: Control (CON), Sham, low potassium dextranglucose (LPD), and AB192 (n=15/group). Orthotopic single LTx was performed in the LPD and AB192 groups. The donor lungs were flush-perfused and preserved with low potassium dextranglucose (LPD) or LPD+CD26/DPP-4 catalytic inhibitor (AB192)...
December 2016: Acta Cirúrgica Brasileira
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