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Bleomycin pulmonary fibrosis

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https://www.readbyqxmd.com/read/28526615/lung-inflammation-after-bleomycin-treatment-in-mice-selection-of-an-accurate-normalization-strategy-for-gene-expression-analysis-in-an-ex-vivo-and-in-vitro-model
#1
Veronica Della Latta, Manuela Cabiati, Silvia Burchielli, Giada Frenzilli, Margherita Bernardeschi, Antonella Cecchettini, Federica Viglione, Maria-Aurora Morales, Silvia Del Ry
Pulmonary fibrosis (PF) is the most common and aggressive interstitial lung disease, characterized by a patchy development of fibrosis leading to progressive destruction of the normal lung architecture which is preceded by an inflammatory process. Gene expression studies are important to understand the development of PF but the accuracy and reproducibility of Real-Time PCR depend on appropriate normalization strategies. This study aimed to analyze the expression variability of eight commonly used reference genes during the initial inflammatory phase of bleomycin-induced PF in a mouse model and to verify whether the selected reference genes could be applied to an in-vitro model of BLM-treated primary murine lung fibroblasts...
May 16, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28506908/effects-of-the-fibroblast-activation-protein-inhibitor-pt100-in-a-murine-model-of-pulmonary-fibrosis
#2
Christine Egger, Catherine Cannet, Christelle Gérard, Thomas Suply, Iwona Ksiazek, Elizabeth Jarman, Nicolau Beckmann
Bleomycin (BLM) induced lung injury is detectable in C57BL/6 mice using magnetic resonance imaging (MRI). We investigated the effects of the fibroblast activation protein (FAP) inhibitor, PT100, in this model. BLM (0.5 mg/kg/day) was administered on days -7, -6, -5, -2, -1, 0 in the nostrils of male mice. PT100 (40 µg/mouse) or vehicle (0.9%NaCl) was dosed per os twice daily from day 1 to 14. MRI was performed before BLM and at days 0, 7 and 14. After the last MRI acquisition, animals were euthanised and the lungs harvested for histological and quantitative real-time polymerase chain reaction (qRT-PCR) analyses...
May 12, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28498407/respiratory-syncytial-virus-infection-accelerates-lung-fibrosis-through-the-unfolded-protein-response-in-a-bleomycin-induced-pulmonary-fibrosis-animal-model
#3
Lina Wang, Wei Cheng, Zhimin Zhang
Emerging evidence has demonstrated that endoplasmic reticulum stress (ER) is involved in the pathogenesis of idiopathic pulmonary fibrosis, however, the underlying mechanism remains unclear. Viral infection often triggers a hyperinflammatory response by an expansion of the ER. The present study was designed to observe the role of respiratory syncytial virus infection (RSV)‑induced ER stress on lung fibrosis. In order to determine the role of ER stress on the onset and progression of pulmonary fibrosis, mice received an intratracheal combined injection of RSV and bleomycin on day 0...
May 10, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28493530/m2-macrophages-induce-emt-through-the-tgf-%C3%AE-smad2-signaling-pathway
#4
Liangying Zhu, Xiao Fu, Xiang Chen, Xiaodong Han, Ping Dong
IPF is characterized by fibroblast accumulation, collagen deposition and ECM remodeling, with myofibroblasts believed to be the effector cell type. Myofibroblasts develop due to EMT of lung alveolar epithelial cells, which can be induced by TGF-β. M2 macrophages, a macrophage subpopulation, secrete large amounts of TGF-β. To clarify the relationship between IPF, EMT, TGF-β and M2 macrophages, a bleomycin-induced pulmonary fibrosis mouse model was used. Seventeen days after mice were treated with bleomycin, the successful establishment of a pulmonary fibrosis model was confirmed by HE stain and Masson's trichrome stain...
May 11, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28488693/icos-protects-against-mortality-from-acute-lung-injury-through-activation-of-il-5-ilc2s
#5
C L Hrusch, S T Manns, D Bryazka, J Casaos, C A Bonham, M R Jaffery, K M Blaine, K A M Mills, P A Verhoef, A O Adegunsoye, J W Williams, M Y Tjota, T V Moore, M E Strek, I Noth, A I Sperling
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease causing irreversible lung scarring and loss of pulmonary function. IPF Patients suffer from a high rate of pulmonary infections and acute exacerbations of disease that further contribute to pulmonary decline. Low expression of the inducible T-cell costimulatory molecule (ICOS) in peripheral blood mononuclear cells predicts decreased survival of IPF patients, but the mechanisms by which ICOS protects are unclear. Using a model of bleomycin-induced lung injury and fibrosis, we now demonstrate that ICOS expression enhances survival from lung injury rather than regulating fibrogenesis...
May 10, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28487960/sulforaphane-prevents-bleomycin%C3%A2-induced-pulmonary-fibrosis-in-mice-by-inhibiting-oxidative-stress-via-nuclear-factor-erythroid-2%C3%A2-related-factor%C3%A2-2-activation
#6
Bingdi Yan, Zhongsen Ma, Shaomin Shi, Yuxin Hu, Tiangang Ma, Gao Rong, Junling Yang
Lung fibrosis is associated with inflammation, apoptosis and oxidative damage. The transcription factor nuclear factor erythroid 2‑related factor‑2 (Nrf2) prevents damage to cells from oxidative stress by regulating the expression of antioxidant proteins. Sulforaphane (SFN), an Nrf2 activator, additionally regulates excessive oxidative stress by promoting the expression of endogenous antioxidants. The present study investigated if SFN protects against lung injury induced by bleomycin (BLM). The secondary aim of the present study was to assess if this protection mechanism involves upregulation of Nrf2 and its downstream antioxidants...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28487375/pulmonary-fibrosis-requires-cell-autonomous-mesenchymal-fibroblast-growth-factor-fgf-signaling
#7
Robert D Guzy, Ling Li, Craig Smith, Samuel J Dorry, Hyun Young Koo, Lin Chen, David M Ornitz
Idiopathic Pulmonary Fibrosis (IPF) is characterized by progressive pulmonary scarring, decline in lung function, and often results in death within three to five years after diagnosis. Fibroblast Growth Factor (FGF) signaling has been implicated in the pathogenesis of IPF; however, the mechanism through which FGF signaling contributes to pulmonary fibrosis remains unclear. We hypothesized that FGF receptor (FGFR) signaling in fibroblasts is required for the fibrotic response to bleomycin. To test this, mice with mesenchyme-specific tamoxifen-inducible inactivation of FGF receptors 1, 2, and 3 (Col1α2-CreER; TCKO mice) were lineage labeled and administered intratracheal bleomycin...
May 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28483669/mechanisms-of-pulmonary-fibrosis-induced-by-core-fucosylation-in-pericytes
#8
Wei Sun, HaiYing Tang, Lili Gao, Xiuna Sun, Jia Liu, WeiDong Wang, Taihua Wu, Hongli Lin
Pulmonary fibrosis is a common outcome of a variety of pulmonary interstitial diseases, and myofibroblasts are the main culprit for this process. Recent studies have found that pericytes are one of the major sources of myofibroblasts; the transformation of which involves a complex process of activation of TGF-β/Smad2/3 and PDGFβ/Erk signaling pathways. We have reported that the transforming growth factor-β receptor and platelet-derived growth factor-β receptor (TGF-βR I and PDGFβR, respectively) are modified by glycosylation...
May 5, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28476015/synergistic-protection-of-schizandrin-b-and-glycyrrhizic-acid-against-bleomycin-induced-pulmonary-fibrosis-by-inhibiting-tgf-%C3%AE-1-smad2-pathways-and-overexpression-of-nox4
#9
Di Zhang, Bin Liu, Bo Cao, Fei Wei, Xin Yu, Guo-Feng Li, Hong Chen, Lu-Qing Wei, Pei-Lan Wang
Pulmonary fibrosis, a progressive and lethal lung disease, is a major therapeutic challenge for which new therapeutic strategies are warranted. Schisandrin B (Sch B) and Glycyrrhizic acid (GA) are the principal active ingredients of Schisandra chinensis and Glycyrrhiza glabra respectively, which have been reported to protect against lung injures. The present study was aimed at exploring the combinatorial therapeutic effects on bleomycin-induced pulmonary fibrosis. Lung fibrotic injuries were induced in mice by a single intratracheal instillation of 5mg/kg bleomycin (BLM)...
May 2, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28469786/mln4924-protects-against-bleomycin-induced-pulmonary-fibrosis-by-inhibiting-the-early-inflammatory-process
#10
Qi Deng, Jiaojiao Zhang, Yaqun Gao, Xiaofei She, Yunchao Wang, Yilin Wang, Xin Ge
Pulmonary fibrosis is a complex pathological process characterized by massive destruction of the structure of lung tissues and aggravated pulmonary function impairment. The underlying mechanisms of pulmonary fibrosis are incompletely understood and therefore limited treatment options are available currently. Here, we report that MLN4924, an NEDD8 activation enzyme (NAE) activity-inhibiting molecule, blocks the maintenance and progression of established pulmonary fibrosis. We found that MLN4924 acts against bleomycin-induced pulmonary fibrosis mainly at the early inflammatory stage...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28467787/the-histone-deacetylase-inhibitor-romidepsin-as-a-potential-treatment-for-pulmonary-fibrosis
#11
Franco Conforti, Elizabeth R Davies, Claire J Calderwood, Thomas H Thatcher, Mark G Jones, David E Smart, Sumeet Mahajan, Aiman Alzetani, Tom Havelock, Toby M Maher, Philip L Molyneaux, Andrew J Thorley, Teresa D Tetley, Jane A Warner, Graham Packham, A Ganesan, Paul J Skipp, Benjamin J Marshall, Luca Richeldi, Patricia J Sime, Katherine M A O'Reilly, Donna E Davies
Idiopathic pulmonary fibrosis (IPF) is a progressive disease that usually affects elderly people. It has a poor prognosis and there are limited therapies. Since epigenetic alterations are associated with IPF, histone deacetylase (HDAC) inhibitors offer a novel therapeutic strategy to address the unmet medical need. This study investigated the potential of romidepsin, an FDA-approved HDAC inhibitor, as an anti-fibrotic treatment and evaluated biomarkers of target engagement that may have utility in future clinical trials...
April 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28466866/posttreatment-with-protectin-dx-ameliorates-bleomycin-induced-pulmonary-fibrosis-and-lung-dysfunction-in-mice
#12
Hui Li, Yu Hao, Huawei Zhang, Weiyang Ying, Dan Li, Yahe Ge, Binyu Ying, Bihuan Cheng, Qingquan Lian, Shengwei Jin
Protectin DX (10S,17S-dihydroxydocosa-4Z,7Z,11E,13Z,15E,19Z-hexaenoic acid) (PDX), generated from Ω-3 fatty docosahexaenoic acids, is believed to exert anti-inflammatory and proresolution bioactions. To date, few studies have been performed regarding its effect on pulmonary fibrosis. Herein we show that PDX exerts a potential therapeutic effect which is distinct from its anti-inflammation and pro-resolution activity on mice with pulmonary fibrosis. In the present study, we showed that bleomycin (BLM) increased inflammatory infiltration, collagen deposition, and lung dysfunction on day7 after challenged in mice...
May 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28463231/disruption-of-lineage-specification-in-adult-pulmonary-mesenchymal-progenitor-cells-promotes-microvascular-dysfunction
#13
Christa F Gaskill, Erica J Carrier, Jonathan A Kropski, Nathaniel C Bloodworth, Swapna Menon, Robert F Foronjy, M Mark Taketo, Charles C Hong, Eric D Austin, James D West, Anna L Means, James E Loyd, W David Merryman, Anna R Hemnes, Stijn De Langhe, Timothy S Blackwell, Dwight J Klemm, Susan M Majka
Pulmonary vascular disease is characterized by remodeling and loss of microvessels and is typically attributed to pathological responses in vascular endothelium or abnormal smooth muscle cell phenotypes. We have challenged this understanding by defining an adult pulmonary mesenchymal progenitor cell (MPC) that regulates both microvascular function and angiogenesis. The current understanding of adult MPCs and their roles in homeostasis versus disease has been limited by a lack of genetic markers with which to lineage label multipotent mesenchyme and trace the differentiation of these MPCs into vascular lineages...
May 2, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28459387/an-official-american-thoracic-society-workshop-report-use-of-animal-models-for-the-preclinical-assessment-of-potential-therapies-for-pulmonary-fibrosis
#14
R Gisli Jenkins, Bethany B Moore, Rachel C Chambers, Oliver Eickelberg, Melanie Königshoff, Martin Kolb, Geoffrey J Laurent, Carmel B Nanthakumar, Mitchell A Olman, Annie Pardo, Moises Selman, Dean Sheppard, Patricia J Sime, Andrew M Tager, Amanda L Tatler, Victor J Thannickal, Eric S White
Numerous compounds have shown efficacy in limiting development of pulmonary fibrosis using animal models, yet few of these compounds have replicated these beneficial effects in clinical trials. Given the challenges associated with performing clinical trials in patients with idiopathic pulmonary fibrosis (IPF), it is imperative that preclinical data packages be robust in their analyses and interpretations to have the best chance of selecting promising drug candidates to advance to clinical trials. The American Thoracic Society has convened a group of experts in lung fibrosis to discuss and formalize recommendations for preclinical assessment of antifibrotic compounds...
May 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28456608/chronic-intermittent-hypoxia-worsens-bleomycin-induced-lung-fibrosis-in-rats
#15
Rudolf K Braun, Oleg Broytman, Felix M Braun, Jacqueline A Brinkman, Andrew Clithero, Dhruvangkumar Modi, David F Pegelow, Marlowe Eldridge, Mihaela Teodorescu
Obstructive sleep apnea (OSA) has been linked to increased mortality in pulmonary fibrosis. Its key feature, chronic intermittent hypoxia (CIH), can lead to oxidative stress and inflammation, known to lead to fibrotic pathology in other organs. We tested the effects of CIH in an animal model of bleomycin-induced lung fibrosis. Sprague Dawley rats were instilled intratracheally with bleomycin (Blm) or saline (Sal), and exposed to CIH or normal air (Norm) for 9 or 30 days. Pulmonary function was tested and lungs were harvested for histological and molecular analyses...
April 26, 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/28455433/akt2-regulates-pulmonary-inflammation-and-fibrosis-via-modulating-macrophage-activation
#16
Yunjuan Nie, Lei Sun, Yaxian Wu, Yaoyao Yang, Jun Wang, Huiqiong He, Yudong Hu, Yanhua Chang, Qing Liang, Jianwei Zhu, Richard D Ye, John W Christman, Feng Qian
Idiopathic pulmonary fibrosis (IPF) is a highly lethal pathological process that is characterized by inflammation, fibroblast accumulation, and excessive collagen deposition. Although AKT2-mediated signaling pathways modulate inflammatory responses, their role in IPF has not been defined. We report that AKT2 deficiency (Akt2(-/-)) protected against bleomycin-induced pulmonary fibrosis and inflammation. Adoptive transfer of wild-type macrophages or administration of IL-13 to Akt2(-/-) mice could restore pulmonary fibrosis...
April 28, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28450283/surfactant-replacement-therapy-reduces-acute-lung-injury-and-collapse-induration-related-lung-remodeling-in-the-bleomycin-model
#17
Lilian Steffen, Clemens Ruppert, Heinz-Gerd Hoymann, Manuela Funke, Simone Ebener, Christina Kloth, Christian Mühlfeld, Matthias Ochs, Lars Knudsen, Elena Lopez-Rodriguez
Bleomycin-induced lung injury leads to surfactant dysfunction and permanent loss of alveoli due to a remodeling process called collapse induration. Collapse induration also occurs in acute interstitial lung disease and idiopathic pulmonary fibrosis in humans. We hypothesized that surfactant dysfunction aggravates lung injury and early remodeling resulting in collapse induration within 7 days after lung injury. Rats received bleomycin to induce lung injury and either repetitive surfactant replacement therapy (SRT: 100mg Curosurf®/kg BW=surf group)) or saline (0...
April 27, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28446589/antifibrotic-effects-of-cyclosporine-a-on-tgf-%C3%AE-1-treated-lung-fibroblasts-and-lungs-from-bleomycin-treated-mice-role-of-hypoxia-inducible-factor-1%C3%AE
#18
Risa Yamazaki, Yoshitoshi Kasuya, Tetsuo Fujita, Hiroki Umezawa, Madoka Yanagihara, Hiroyuki Nakamura, Ichiro Yoshino, Koichiro Tatsumi, Toshihiko Murayama
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disorder that is characterized by aberrant tissue remodeling and the formation of fibroblastic foci that are composed of fibrogenic myofibroblasts. TGF-β1 is one of the factors that are responsible for fibrosis as it promotes fibroblast to myofibroblast differentiation (FMD) and is associated with up-regulation of α-smooth muscle actin. Therefore, inhibition of FMD may represent an effective strategy for the treatment of IPF. Here, we describe the treatment of human lung fibroblasts (WI-38 and HFL-1 cells) with cyclosporine A (CsA), which reduces TGF-β1-induced FMD via degradation of hypoxia-inducible factor-1α (HIF-1α)...
April 26, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28434932/combinatorial-treatment-of-idiopathic-pulmonary-fibrosis-using-nanoparticles-with-prostaglandin-e-and-sirna-s
#19
O B Garbuzenko, V Ivanova, V Kholodovych, D C Reimer, K R Reuhl, E Yurkow, D Adler, T Minko
Inhalation delivery of prostaglandin E (PGE2) in combination with selected siRNA(s) was proposed for the efficient treatment of idiopathic pulmonary fibrosis (IPF). Nanostructured lipid carriers (NLC) were used as a delivery system for PGE2 with and without siRNAs targeted to MMP3, CCL12, and HIF1Alpha mRNAs. The model of IPF was developed in SKH1 mice by intratracheal administration of bleomycin at a dose of 1.5U/kg. Results showed that NLC-PGE2 in combination with three siRNAs delivered locally to the lungs by inhalation markedly reduced mouse body mass, substantially limited hydroxyproline content in the lungs and disturbances of the mRNAs and protein expression, restricted lung tissue damage and prevented animal mortality...
April 19, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28422760/cannabinoid-cb1-receptor-overactivity-contributes-to-the-pathogenesis-of-idiopathic-pulmonary-fibrosis
#20
Resat Cinar, Bernadette R Gochuico, Malliga R Iyer, Tony Jourdan, Tadafumi Yokoyama, Joshua K Park, Nathan J Coffey, Hadass Pri-Chen, Gergő Szanda, Ziyi Liu, Ken Mackie, William A Gahl, George Kunos
Idiopathic pulmonary fibrosis (IPF) is a life-threatening disease without effective treatment, highlighting the need for identifying new targets and treatment modalities. The pathogenesis of IPF is complex, and engaging multiple targets simultaneously might improve therapeutic efficacy. To assess the role of the endocannabinoid/cannabinoid receptor 1 (endocannabinoid/CB1R) system in IPF and its interaction with inducible nitric oxide synthase (iNOS) as dual therapeutic targets, we analyzed lung fibrosis and the status of the endocannabinoid/CB1R system and iNOS in mice with bleomycin-induced pulmonary fibrosis (PF) and in lung tissue and bronchoalveolar lavage fluid (BALF) from patients with IPF, as well as controls...
April 20, 2017: JCI Insight
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