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Bleomycin pulmonary fibrosis

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https://www.readbyqxmd.com/read/29297621/amnion-epithelial-cell-derived-exosomes-restrict-lung-injury-and-enhance-endogenous-lung-repair
#1
Jean L Tan, Sin N Lau, Bryan Leaw, Hong P T Nguyen, Lois A Salamonsen, Mohamed I Saad, Siow T Chan, Dandan Zhu, Mirja Krause, Carla Kim, William Sievert, Euan M Wallace, Rebecca Lim
Idiopathic pulmonary fibrosis (IPF) is characterized by chronic inflammation, severe scarring, and stem cell senescence. Stem cell-based therapies modulate inflammatory and fibrogenic pathways by release of soluble factors. Stem cell-derived extracellular vesicles should be explored as a potential therapy for IPF. Human amnion epithelial cell-derived exosomes (hAEC Exo) were isolated and compared against human lung fibroblasts exosomes. hAEC Exo were assessed as a potential therapy for lung fibrosis. Exosomes were isolated and evaluated for their protein and miRNA cargo...
January 3, 2018: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29290631/emodin-attenuates-bleomycin-induced-pulmonary-fibrosis-via-anti-inflammatory-and-anti-oxidative-activities-in-rats
#2
Sheng-Lan Tian, Yang Yang, Xiao-Liu Liu, Qing-Bang Xu
BACKGROUND Idiopathic pulmonary fibrosis (IPF) can severely damage lung function, which may result in death. Emodin is a major ingredient of rhubarb and has been proven to protect against lung disruptions. Our study focused on the potential medicinal effect of emodin against IPF. MATERIAL AND METHODS The experiment subjects were fully-grown male Sprague-Dawley rats with average weight of 180-220 kg. Histological analyses, Western blotting analysis, quantitative real-time PCR, and statistical analysis were used in the study...
January 1, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29283216/a-lipidomics-approach-to-identifying-key-lipid-species-involved-in-vegf-inhibitor-mediated-attenuation-of-bleomycin-induced-pulmonary-fibrosis
#3
Yogesh M Kulkarni, Sucharita Dutta, Anand Krishnan V Iyer, Clayton A Wright, Vani Ramesh, Vivek Kaushik, Oliver John Semmes, Neelam Azad
PURPOSE: Poor molecular characterization of idiopathic pulmonary fibrosis (IPF) has led to insufficient understanding of the pathogenesis of the disease, resulting in lack of effective therapies and poor prognosis. Particularly, the role of lipid imbalance due to impaired lipid metabolism in the pathogenesis of IPF has been poorly studied. EXPERIMENTAL DESIGN: We have used shotgun lipidomics in a bleomycin (BLM) mouse model of pulmonary fibrosis with vascular endothelial growth factor (VEGF)-inhibitor CBO-P11 as a therapeutic measure, to identify a comprehensive set of lipids that contribute to the pathogenesis of pulmonary fibrosis...
December 28, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/29279415/leucine-rich-%C3%AE-2-glycoprotein-promotes-lung-fibrosis-by-modulating-tgf-%C3%AE-signaling-in-fibroblasts
#4
Hiromi Honda, Minoru Fujimoto, Satoshi Serada, Hayato Urushima, Takashi Mishima, Hyun Lee, Tomoharu Ohkawara, Nobuoki Kohno, Noboru Hattori, Akihito Yokoyama, Tetsuji Naka
TGF-β has an important role in fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). Detailed analysis of TGF-β signaling in pulmonary fibrosis at the molecular level is needed to identify novel therapeutic targets. Recently, leucine-rich alpha-2 glycoprotein (LRG) was reported to function as a modulator of TGF-β signaling in angiogenesis and tumor progression. However, the involvement of LRG in fibrotic disorders, including IPF, has not yet been investigated. In this study, we investigated the role of LRG in fibrosis by analyzing LRG knockout (KO) mice with bleomycin-induced lung fibrosis, an animal model of pulmonary fibrosis...
December 2017: Physiological Reports
https://www.readbyqxmd.com/read/29278701/gentiopicroside-ameliorates-bleomycin-induced-pulmonary-fibrosis-in-mice-via-inhibiting-inflammatory-and-fibrotic-process
#5
Cheng Chen, Yong-Yan Wang, Ying-Xia Wang, Meng-Qun Cheng, Jian-Bing Yin, Xuan Zhang, Zhi-Peng Hong
Pulmonary fibrosis (PF) is a chronic and ultimately fatal interstitial lung disease of various causes. The advent of nintedanib and pirfenidone provides treatment options for PF patients for the first time. However, the adverse effects of the two drugs such as gastrointestinal disorders and hepatic dysfunction often lead to treatment discontinuation. Gentiopicroside (GPS) is a natural secoiridoid glycoside from gentian species of medicinal plants, and has a variety of pharmacological activities, including hepatoprotective and cholagogic, anti-inflammatory, antinociceptive, and smooth muscle relaxing activities...
December 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29239818/inhibitory-effect-of-compound-chuanxiong-kangxian-granules-on-bleomycin-induced-pulmonary-fibrosis-in-rats
#6
Weiyi Shi, Bo Feng, Shuguang Xu, Xiaoyun Shen, Tiefeng Zhang
BACKGROUND: The diverse medicinal properties of herbal compounds make them suitable candidates to treat multifactorial conditions such as pulmonary fibrosis. We investigated the effects and mechanisms of compound Chuanxiong Kangxian granules (CCKG) on a bleomycin (BLM)-induced pulmonary fibrosis model in rats. METHODS AND RESULTS: Following an intratracheal instillation of BLM, Sprague Dawley rats were intragastrically administrated with different doses of CCKG solution or hydrocortisone for 28 d, while control and BLM-treated rats were administered with saline solution...
November 24, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29220597/dietary-nacl-affects-bleomycin-induced-lung-fibrosis-in-mice
#7
Wensheng Chen, Darrell Pilling, Richard H Gomer
PURPOSE: High levels of NaCl in the diet are associated with both cardiac and renal fibrosis, but whether salt intake affects pulmonary fibrosis has not been examined. AIM OF THE STUDY: To test the hypothesis that salt intake might affect pulmonary fibrosis. MATERIALS AND METHODS: Mice were fed low, normal, or high salt diets for 2 weeks, and then treated with oropharyngeal bleomycin to induce pulmonary fibrosis, or oropharyngeal saline as a control...
December 8, 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/29220578/pd-1-pd-l1-pathway-mediates-the-alleviation-of-pulmonary-fibrosis-by-human-mesenchymal-stem-cells-in-humanized-mice
#8
Ke Ni, Ming Liu, Jian Zheng, Liyan Wen, Qingyun Chen, Zheng Xiang, Kowk-Tai Lam, Yinping Liu, Godfrey Chi-Fung Chan, Yu-Lung Lau, Wenwei Tu
RATIONALE: Pulmonary fibrosis is a chronic progressive lung disease with few treatments. Human mesenchymal stem cells (MSC) have been shown to be beneficial to pulmonary fibrosis as they have the immunomodulatory capacity. However, there is no reliable model to test the therapeutic effect of human MSC in vivo. METHODS: Here, to mimic pulmonary fibrosis in humans, we established a novel bleomycin-induced pulmonary fibrosis model in humanized mice. Based on this model, the benefit of human MSC to pulmonary fibrosis and underlying mechanism were investigated...
December 8, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29217661/foxo3-an-important-player-in-fibrogenesis-and-therapeutic-target-for-idiopathic-pulmonary-fibrosis
#9
Hamza M Al-Tamari, Swati Dabral, Anja Schmall, Pouya Sarvari, Clemens Ruppert, Jihye Paik, Ronald A DePinho, Friedrich Grimminger, Oliver Eickelberg, Andreas Guenther, Werner Seeger, Rajkumar Savai, Soni S Pullamsetti
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal parenchymal lung disease with limited therapeutic options, with fibroblast-to-myofibroblast transdifferentiation and hyperproliferation playing a major role. Investigating ex vivo-cultured (myo)fibroblasts from human IPF lungs as well as fibroblasts isolated from bleomycin-challenged mice, Forkhead box O3 (FoxO3) transcription factor was found to be less expressed, hyperphosphorylated, and nuclear-excluded relative to non-diseased controls. Downregulation and/or hyperphosphorylation of FoxO3 was reproduced by exposure of normal human lung fibroblasts to various pro-fibrotic growth factors and cytokines (FCS, PDGF, IGF1, TGF-β1)...
December 7, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29212801/roles-of-high-mobility-group-box-1-and-thrombin-in-murine-pulmonary-fibrosis-and-the-therapeutic-potential-of-thrombomodulin
#10
Takashi Kida, Takahiro Seno, Hidetake Nagahara, Takuya Inoue, Amane Nakabayashi, Yuji Kukida, Kazuki Fujioka, Wataru Fujii, Makoto Wada, Masataka Kohno, Yutaka Kawahito
Cross-talk between inflammation and coagulation plays important roles in acute or subacute progressive pulmonary fibrosis characterized by diffuse alveolar damage. Thrombomodulin is a physiological inhibitor of high-mobility group box 1 (HMGB1) and thrombin, and may be effective for this condition. This study investigated the roles of HMGB1 and thrombin in the pathophysiology of bleomycin-induced pulmonary fibrosis and the efficacy of recombinant human soluble thrombomodulin (rhTM). Pulmonary fibrosis was induced in wild-type C57BL/6 mice by intratracheal instillation of bleomycin...
December 6, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29211497/the-rho-kinase-isoforms-rock1-and-rock2-each-contribute-to-the-development-of-experimental-pulmonary-fibrosis
#11
Rachel S Knipe, Clemens K Probst, David Lagares, Alicia Franklin, Jillian J Spinney, Patricia L Brazee, Paula Grasberger, Linlin Zhang, Katharine E Black, Norihiko Sakai, Barry S Shea, James K Liao, Benjamin D Medoff, Andrew M Tager
Pulmonary fibrosis is thought to result from dysregulated wound repair after repetitive lung injury. Many cellular responses to injury involve rearrangements of the actin cytoskeleton mediated by the two isoforms of the Rho-associated coiled coil forming protein kinase, ROCK1 and ROCK2. Additionally, profibrotic mediators such as transforming growth factor-beta (TGF-β), thrombin and lysophosphatidic acid (LPA) act through receptors that activate ROCK. Inhibition of ROCK activation may be a potent therapeutic strategy for human pulmonary fibrosis...
December 6, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29206498/the-potential-application-of-strategic-released-apigenin-from-polymeric-carrier-in-pulmonary-fibrosis
#12
Junxia Zhang, Liqin Chao, Xianghua Liu, Yanmei Shi, Caili Zhang, Lingfei Kong, Ruiqin Li
AIM: The capability of reducing fibrotic and inflammatory responses in lung tissues represents a gold standard for evaluating the efficacy of therapeutic interventions for treating idiopathic pulmonary fibrosis (IPF). A wide variety of therapeutic strategies have been employed in clinic to treat PF, but limited success has been obtained. Apigenin (4, 5, 7-trihydroxyflavone) is a member of flavonoid family that exerts anti-inflammatory and anti-fibrosis effects. In this study, we explore the potential therapeutic effect of apigenin in lung fibrosis...
December 5, 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/29203799/essential-involvement-of-the-cx3cl1-cx3cr1-axis-in-bleomycin-induced-pulmonary-fibrosis-via-regulation-of-fibrocyte-and-m2-macrophage-migration
#13
Yuko Ishida, Akihiko Kimura, Mizuho Nosaka, Yumi Kuninaka, Hiroaki Hemmi, Izumi Sasaki, Tsuneyasu Kaisho, Naofumi Mukaida, Toshikazu Kondo
The potential role of macrophages in pulmonary fibrosis (PF) prompted us to evaluate the roles of CX3CR1, a chemokine receptor abundantly expressed in macrophages during bleomycin (BLM)-induced PF. Intratracheal BLM injection induced infiltration of leukocytes such as macrophages into the lungs, which eventually resulted in fibrosis. CX3CR1 expression was mainly detected in the majority of macrophages and in a small portion of α-smooth muscle actin-positive cells in the lungs, while CX3CL1 was expressed in macrophages...
December 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29200204/thyroid-hormone-inhibits-lung-fibrosis-in-mice-by-improving-epithelial-mitochondrial-function
#14
Guoying Yu, Argyris Tzouvelekis, Rong Wang, Jose D Herazo-Maya, Gabriel H Ibarra, Anup Srivastava, Joao Pedro Werneck de Castro, Giuseppe DeIuliis, Farida Ahangari, Tony Woolard, Nachelle Aurelien, Rafael Arrojo E Drigo, Ye Gan, Morven Graham, Xinran Liu, Robert J Homer, Thomas S Scanlan, Praveen Mannam, Patty J Lee, Erica L Herzog, Antonio C Bianco, Naftali Kaminski
Thyroid hormone (TH) is critical for the maintenance of cellular homeostasis during stress responses, but its role in lung fibrosis is unknown. Here we found that the activity and expression of iodothyronine deiodinase 2 (DIO2), an enzyme that activates TH, were higher in lungs from patients with idiopathic pulmonary fibrosis than in control individuals and were correlated with disease severity. We also found that Dio2-knockout mice exhibited enhanced bleomycin-induced lung fibrosis. Aerosolized TH delivery increased survival and resolved fibrosis in two models of pulmonary fibrosis in mice (intratracheal bleomycin and inducible TGF-β1)...
December 4, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29185215/nickle-ii-ions-exacerbate-bleomycin-induced-pulmonary-inflammation-and-fibrosis-by-activating-the-ros-akt-signaling-pathway
#15
Lawei Yang, Ziying Lin, Yahong Wang, Chunyan Li, Wenya Xu, Qinglan Li, Weimin Yao, Zeqing Song, Gang Liu
Nickle (Ni) is a heavy metal found in particulate matter. We previously reported that Ni ions are strongly associated with high apoptosis rates and high expression of IL-1β in human bronchial epithelial cells following exposure to PM2.5; however, the effects of Ni ions on pulmonary fibrosis have not been fully elucidated. In the current study, we evaluated whether Ni ions can exacerbate bleomycin (BLM)-induced pulmonary fibrosis in a mouse model and illustrated the potential mechanism. Ni ions inhibited cell proliferation and induced apoptosis in A549 and MRC-5 cells...
November 28, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29175452/changes-in-expression-of-cytokines-in-polyhexamethylene-guanidine-induced-lung-fibrosis-in-mice-comparison-of-bleomycin-induced-lung-fibrosis
#16
Min-Seok Kim, Sung-Hwan Kim, Doin Jeon, Hyeon-Young Kim, Kyuhong Lee
Inhalation of polyhexamethylene guanidine (PHMG) causes irreversible pulmonary injury, such as pulmonary fibrosis. However, the mechanism underlying PHMG-induced lung injury is unclear. In this study, we compared the difference in time-dependent lung injury between PHMG- and bleomycin (BLM)-treated mice and determined cytokines involved in inducing lung injury by performing cytokine antibody array analysis. Mice were treated once with 1.8mg/kg BLM or 1.2mg/kg PHMG through intratracheal instillation and were sacrificed on days 7 and 28...
November 22, 2017: Toxicology
https://www.readbyqxmd.com/read/29172997/identification-of-anxa2-annexin-a2-as-a-specific-bleomycin-target-to-induce-pulmonary-fibrosis-by-impeding-tfeb-mediated-autophagic-flux
#17
Kui Wang, Tao Zhang, Yunlong Lei, Xuefeng Li, Jingwen Jiang, Jiang Lan, Yuan Liu, Haining Chen, Wei Gao, Na Xie, Qiang Chen, Xiaofeng Zhu, Xiang Liu, Ke Xie, Yong Peng, Edouard C Nice, Min Wu, Canhua Huang, Yuquan Wei
Bleomycin is a clinically potent anticancer drug used for the treatment of germ-cell tumors, lymphomas and squamous-cell carcinomas. Unfortunately, the therapeutic efficacy of bleomycin is severely hampered by the development of pulmonary fibrosis. However, the mechanisms underlying bleomycin-induced pulmonary fibrosis, particularly the molecular target of bleomycin, remains unknown. Here, using a chemical proteomics approach, we identify ANXA2 (annexin A2) as a direct binding target of bleomycin. The interaction of bleomycin with ANXA2 was corroborated both in vitro and in vivo...
November 26, 2017: Autophagy
https://www.readbyqxmd.com/read/29172151/oxidative-stress-driven-pulmonary-inflammation-and-fibrosis-in-a-mouse-model-of-human-ataxia-telangiectasia
#18
Ruth Duecker, Patrick Baer, Olaf Eickmeier, Maja Strecker, Jennifer Kurz, Alexander Schaible, Dirk Henrich, Stefan Zielen, Ralf Schubert
Lung failure is responsible for significant morbidity and is a frequent cause of death in ataxia-telangiectasia (A-T). Disturbance in the redox balance of alveolar epithelial cells must be considered as a causal factor for respiratory disease in A-T. To investigate bronchoalveolar sensitivity to reactive oxygen species (ROS) and ROS-induced DNA damage, we used bleomycin (BLM) to induce experimental inflammation and fibrotic changes in the Atm-deficient mouse model. BLM or saline was administered by oropharyngeal instillation into the lung of Atm-deficient mice and wild-type mice...
November 10, 2017: Redox Biology
https://www.readbyqxmd.com/read/29167193/airway-transplantation-of-adipose-stem-cells-protects-against-bleomycin-induced-pulmonary-fibrosis
#19
Pedro Llontop, Daniel Lopez-Fernandez, Bernardino Clavo, Juan Luis Afonso Martín, María D Fiuza-Pérez, Mariano García Arranz, Joaquín Calatayud, Laureano Molins López-Rodó, Khalid Alshehri, Adil Ayub, Wissam Raad, Faiz Bhora, Norberto Santana-Rodríguez
Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with poor prognosis. Adipose-derived stem cells (ADSC) have demonstrated regenerative properties in several tissues. The hypothesis of this study was that airway transplantation of ADSC could protect against bleomycin (BLM)-induced pulmonary fibrosis (PF). Fifty-eight lungs from 29 male Sprague-Dawley rats were analyzed. Animals were randomly divided into five groups: a) control (n=3); b) sham (n=6); c) BLM (n=6); d) BLM+ADSC-2d (n=6); and e) BLM+ADSC-14d (n=8)...
November 21, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/29158503/kr%C3%A3-pple-like-factor-4-attenuates-lung-fibrosis-via-inhibiting-epithelial-mesenchymal-transition
#20
Lianjun Lin, Qian Han, Yan Xiong, Ting Li, Zhonghui Liu, Huiying Xu, Yanping Wu, Nanping Wang, Xinmin Liu
Epithelial-mesenchymal transition (EMT) plays an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Krüpple-like-factor 4 (KLF4), has been suggested to play an important role in the phenotype transition. However, its function in pulmonary fibrosis and EMT of human alveolar epithelial cells (AECs) remains unclear. This study aimed to examine the role of KLF4 in pulmonary fibrosis and EMT. Decreased expression of KLF4 was first observed in human IPF lung tissues and models of bleomycin-induced pulmonary fibrosis...
November 20, 2017: Scientific Reports
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