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Bleomycin pulmonary fibrosis

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https://www.readbyqxmd.com/read/29782549/sphingosine-1-phosphate-receptor-2-facilitates-pulmonary-fibrosis-through-potentiating-il-13-pathway-in-macrophages
#1
Juanjuan Zhao, Yasuo Okamoto, Yuya Asano, Kazuhiro Ishimaru, Sho Aki, Kazuaki Yoshioka, Noriko Takuwa, Takashi Wada, Yutaka Inagaki, Chiaki Takahashi, Takumi Nishiuchi, Yoh Takuwa
Idiopathic pulmonary fibrosis is a devastating disease with poor prognosis. The pathogenic role of the lysophospholipid mediator sphingosine-1-phosphate and its receptor S1PR2 in lung fibrosis is unknown. We show here that genetic deletion of S1pr2 strikingly attenuated lung fibrosis induced by repeated injections of bleomycin in mice. We observed by using S1pr2LacZ/+ mice that S1PR2 was expressed in alveolar macrophages, vascular endothelial cells and alveolar epithelial cells in the lung and that S1PR2-expressing cells accumulated in the fibrotic legions...
2018: PloS One
https://www.readbyqxmd.com/read/29777878/pulmonary-delivery-of-polyplexes-for-combined-pai-1-gene-silencing-and-cxcr4-inhibition-to-treat-lung-fibrosis
#2
B S Ling Ding, B S Chenfei Zhu, M S Fei Yu, M S Pengkai Wu, M S Gang Chen, B S Aftab Ullah, Kaikai Wang, Minjie Sun, Jing Li, David Oupický
This report describes the development of polyplexes based on CXCR4-inhibiting poly(ethylenimine) derivative (PEI-C) for pulmonary delivery of siRNA to silence plasminogen activator inhibitor-1 (siPAI-1) as a new combination treatment of pulmonary fibrosis (PF). Safety and delivery efficacy of the PEI-C/siPAI-1 polyplexes was investigated in vitro in primary lung fibroblasts isolated from mice with bleomycin-induced PF. Biodistribution analysis following intratracheal administration of fluorescently labeled polyplexes showed prolonged retention in the lungs...
May 16, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29772024/use-of-human-amniotic-epithelial-cells-in-mouse-models-of-bleomycin-induced-lung-fibrosis-a-systematic-review-and-meta-analysis
#3
Fang He, Aiting Zhou, Shuo Feng
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) urgently requires effective treatment. Bleomycin-induced lung injury models are characterized by initial inflammation and secondary fibrosis, consistent with the pathological features of IPF. Human amniotic epithelial cells (hAECs) exhibit good differentiation potential and paracrine activity and are thus ideal for cell-based clinical therapies. The therapeutic effects of hAECs on lung fibrosis are attributed to many factors. We performed a systematic review of preclinical studies investigating the treatment of pulmonary fibrosis with hAECs to provide suggestions for their clinical use...
2018: PloS One
https://www.readbyqxmd.com/read/29770156/probing-into-the-mechanism-of-alkaline-citrus-extract-promoted-apoptosis-in-pulmonary-fibroblasts-of-bleomycin-induced-pulmonary-fibrosis-mice
#4
Qi Wu, Yao Zhou, Fan-Chao Feng, Yi-Han Jin, Zhi-Chao Wang, Xian-Mei Zhou
We extracted the primary pulmonary fibroblasts of the normal and bleomycin-induced pulmonary fibrosis mice and investigated the functioning mechanism of citrus alkaline extract (CAE) in the induction of pulmonary fibroblast apoptosis. The expression intensity of vimentin of the pulmonary fibroblasts in the model mice was higher than that in the normal mice. Meanwhile, the positive expression rate and expression intensity of alpha smooth muscle actin ( α -SMA) of the pulmonary fibroblasts in the model mice were higher than those in the normal mice...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29752961/dihydroartemisinin-alleviates-oxidative-stress-in-bleomycin-induced-pulmonary-fibrosis
#5
Dong-Xia Yang, Jun Qiu, Hui-Hui Zhou, Yan Yu, Dong-Li Zhou, Yan Xu, Ming-Zhe Zhu, Xing-Ping Ge, Jing-Min Li, Chang-Jun Lv, Hong-Qin Zhang, Wen-Dan Yuan
AIMS: Dihydroartemisinin has been shown to inhibit the development of pulmonary fibrosis in rats, but its mechanism has yet to be elucidated. This study aimed to determine the mechanisms of dihydroartemisinin in bleomycin-induced pulmonary fibrosis in a rat model. MAIN METHODS: Morphological changes and collagen deposition were analyzed via hematoxylin-eosin staining and Masson staining and the expression of biotic-factor-related oxidative stress in lung tissues was assayed with standard assay kits...
May 9, 2018: Life Sciences
https://www.readbyqxmd.com/read/29747538/protective-effect-of-standardized-extract-of-myrtus-communis-l-myrtle-on-experimentally-bleomycin-induced-pulmonary-fibrosis-biochemical-and-histopathological-study
#6
Mitra Samareh Fekri, Ali Mandegary, Fariba Sharififar, Hamid Reza Poursalehi, Mohammad Hadi Nematollahi, Atefe Izadi, Mohammad Mehdipour, Amir Asadi, Masoomeh Samareh Fekri
CONTEXT: Myrtle (Myrtus communis L) has been used widely in traditional medicine for different respiratory disorders. Idiopathic pulmonary fibrosis (IPF) is an inflammatory disease characterized by progressive loss of lung function with poor prognosis. The pathogenesis of disease has not been completely elucidated, but probably persistent epithelial damages are involved. OBJECTIVE: Evaluation of biochemical and histopathological effect of preventive and therapeutic doses of myrtle against bleomycin (BLM)-induced pulmonary fibrosis (PF) in animal model...
May 11, 2018: Drug and Chemical Toxicology
https://www.readbyqxmd.com/read/29740320/amifostine-analog-drde-30-attenuates-bleomycin-induced-pulmonary-fibrosis-in-mice
#7
Aastha Arora, Vikas Bhuria, Puja P Hazari, Uma Pathak, Sweta Mathur, Bal G Roy, Rajat Sandhir, Ravi Soni, Bilikere S Dwarakanath, Anant N Bhatt
Bleomycin (BLM) is an effective curative option in the management of several malignancies including pleural effusions; but pulmonary toxicity, comprising of pneumonitis and fibrosis, poses challenge in its use as a front-line chemotherapeutic. Although Amifostine has been found to protect lungs from the toxic effects of radiation and BLM, its application is limited due to associated toxicity and unfavorable route of administration. Therefore, there is a need for selective, potent, and safe anti-fibrotic drugs...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29733296/foxm1-is-a-critical-driver-of-lung-fibroblast-activation-and-fibrogenesis
#8
Loka R Penke, Jennifer M Speth, Vijaya L Dommeti, Eric S White, Ingrid L Bergin, Marc Peters-Golden
While the transcription factor forkhead box M1 (FOXM1) is well known as a proto-oncogene, its potential role in lung fibroblast activation has never been explored. Here, we show that FOXM1 is more highly expressed in fibrotic than in normal lung fibroblasts in humans and mice. FOXM1 was required not only for cell proliferation in response to mitogens, but also for myofibroblast differentiation and apoptosis resistance elicited by TGF-β. The lipid mediator PGE2, acting via cAMP signaling, was identified as an endogenous negative regulator of FOXM1...
May 7, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29731719/rhace2-therapy-modifies-bleomycin-induced-pulmonary-hypertension-via-rescue-of-vascular-remodeling
#9
Anandharajan Rathinasabapathy, Andrew J Bryant, Toshio Suzuki, Christy Moore, Sheila Shay, Santhi Gladson, James D West, Erica J Carrier
Background: Pulmonary hypertension (PH) is a progressive cardiovascular disease, characterized by endothelial and smooth muscle dysfunction and vascular remodeling, followed by right heart failure. Group III PH develops secondarily to chronic lung disease such as idiopathic pulmonary fibrosis (IPF), and both hastens and predicts mortality despite of all known pharmacological interventions. Thus, there is urgent need for development of newer treatment strategies. Objective: Angiotensin converting enzyme 2 (ACE2), a member of the renin angiotensin family, is therapeutically beneficial in animal models of pulmonary vascular diseases and is currently in human clinical trials for primary PH...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29727583/protein-tyrosine-phosphatase-n13-ptpn13-promotes-myofibroblast-resistance-to-apoptosis-in-idiopathic-pulmonary-fibrosis
#10
Alison Bamberg, Elizabeth F Redente, Steve D Groshong, Rubin M Tuder, Carlyne D Cool, Rebecca C Keith, Benjamin L Edelman, Bart P Black, Gregory P Cosgrove, Murry W Wynes, Douglas Curran-Everett, Stijn De Langhe, Luis A Ortiz, Andrew Thorburn, David W H Riches
RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a progressive, fibrotic interstitial lung disease characterized by (myo)fibroblast accumulation and collagen deposition. Resistance to Fas-induced apoptosis is thought to facilitate (myo)fibroblast persistence in fibrotic lung tissues, by poorly understood mechanisms. OBJECTIVES: We tested the hypothesis that protein tyrosine phosphatase PTPN13 is expressed by IPF lung (myo)fibroblasts, promotes their resistance to Fas-induced apoptosis and contributes to the development of pulmonary fibrosis...
May 4, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29725493/intermittent-hypoxia-increases-the-severity-of-bleomycin-induced-lung-injury-in-mice
#11
Thomas Gille, Morgane Didier, Cécile Rotenberg, Eva Delbrel, Dominique Marchant, Angela Sutton, Nicolas Dard, Liasmine Haine, Nicolas Voituron, Jean-François Bernaudin, Dominique Valeyre, Hilario Nunes, Valérie Besnard, Emilie Boncoeur, Carole Planès
Background: Severe obstructive sleep apnea (OSA) with chronic intermittent hypoxia (IH) is common in idiopathic pulmonary fibrosis (IPF). Here, we evaluated the impact of IH on bleomycin- (BLM-) induced pulmonary fibrosis in mice. Methods: C57BL/6J mice received intratracheal BLM or saline and were exposed to IH (40 cycles/hour; FiO2 nadir: 6%; 8 hours/day) or intermittent air (IA). In the four experimental groups, we evaluated (i) survival; (ii) alveolar inflammation, pulmonary edema, lung oxidative stress, and antioxidant enzymes; (iii) lung cell apoptosis; and (iv) pulmonary fibrosis...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29722566/inhibition-of-raf1-ameliorates-bleomycin-induced-pulmonary-fibrosis-through-attenuation-of-tgf%C3%AE-1-signaling
#12
Shuang Li, Jia Liu, Jiangning Tan, Lian Li, Mary J Kaltreider, Jing Zhao, Daniel J Kass, Dong Shang, Yutong Zhao
Idiopathic Pulmonary Fibrosis (IPF) is a fatal fibrotic lung disease associated with aberrant activation and differentiation of fibroblasts, leading to abnormal extracellular matrix (ECM) production. Currently, it is still an untreatable disease except lung transplantation. Here, we demonstrate that the Raf1 inhibitor GW5074 ameliorates lung fibrosis in bleomycin-induced pulmonary fibrosis. Post-treatment with GW5074 reduced fibronectin (FN) expression, collagen deposition, and inflammatory cell infiltration in bleomycin-challenged mice, suggesting an anti-fibrotic property of GW5074...
May 3, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29722562/nmda-receptor-activation-inhibits-the-anti-fibrotic-effect-of-bm-mscs-on-bleomycin-induced-pulmonary-fibrosis
#13
Xiao-Hong Li, Chen Li, Yiting Tang, Yan-Hong Huang, Qing-Mei Cheng, Xiao-Ting Huang, Feiyan Zhao, Cai-Xia Hao, Dan-Dan Feng, Jian-Ping Xu, Jianzhong Han, Siyuan Tang, Wei Liu, Shaojie Yue, Zi-Qiang Luo
Endogenous glutamate (Glu) release and N-methyl-D-aspartate (NMDA) receptor (NMDAR) activation are associated with lung injury in different animal models. However, the underlying mechanism is unclear. Bone marrow-derived mesenchymal stem cells (BM-MSCs), which show potential use for immunomodulation and tissue-protection, play a protective role in pulmonary fibrosis (PF) process. Here, we found the increased Glu release from the BM cells of bleomycin (BLM)-induced PF mice in vivo. BLM stimulation also increased the extracellular Glu in BM-MSCs via the antiporter system xc- in vitro...
May 3, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29722022/an-st2-dependent-role-of-bone-marrow-derived-group-2-innate-lymphoid-cells-in-pulmonary-fibrosis
#14
Yuyue Zhao, Francina Gonzalez De Los Santos, Zhe Wu, Tianju Liu, Sem H Phan
Recent evidence supports that bone marrow (BM)-derived hematopoietic progenitor cells play an important role in lung injury and fibrosis. While these cells give rise to multiple cell types, the ST2 (Il1rl1)-expressing group 2 innate lymphoid cells (ILC2) derived from BM progenitors have been implicated in tissue repair and remodeling, including in lung fibrosis. To further investigate the precise role of BM-derived ILC2 in the pathogenesis of fibrotic lung disease their importance in the bleomycin-induced lung fibrosis model was evaluated by analyzing the effects of selective ST2 deficiency in the BM compartment...
May 3, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29708527/a-multimodal-imaging-approach-based-on-micro-ct-and-fluorescence-molecular-tomography-for-longitudinal-assessment-of-bleomycin-induced-lung-fibrosis-in-mice
#15
Francesca Ruscitti, Francesca Ravanetti, Gaetano Donofrio, Yanto Ridwan, Paula van Heijningen, Jeroen Essers, Gino Villetti, Antonio Cacchioli, Wim Vos, Franco Fabio Stellari
Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by the progressive and irreversible destruction of lung architecture, which causes significant deterioration in lung function and subsequent death from respiratory failure. The pathogenesis of IPF in experimental animal models has been induced by bleomycin administration. In this study, we investigate an IPF-like mouse model induced by a double intratracheal bleomycin instillation. Standard histological assessments used for studying lung fibrosis are invasive terminal procedures...
April 13, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29705800/histone-deacetylases-promote-er-stress-induced-epithelial-mesenchymal-transition-in-human-lung-epithelial-cells
#16
Daishun Liu, Honglan Zhu, Ling Gong, Shenglan Pu, Yang Wu, Wei Zhang, Guichuan Huang
BACKGROUND/AIMS: Epithelial to mesenchymal transition (EMT) is a crucial process involved in pulmonary fibrosis. This study aimed to explore the role of histone deacetylases (HDACs) and endoplasmic reticulum (ER) stress in EMT in human lung epithelial cells. METHODS: Human lung adenocarcinoma A549 cells were treated with bleomycin and tunicamycin to induce EMT. The proliferation of A549 cells was detected by MTT assay. The expression of HDACs and EMT markers was detected by PCR and Western blot analysis...
April 25, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29704504/inhibition-of-mtor-ameliorates-bleomycin-induced-pulmonary-fibrosis-by-regulating-epithelial-mesenchymal-transition
#17
Qian Han, Lianjun Lin, Beilei Zhao, Nanping Wang, Xinmin Liu
Epithelial-mesenchymal transition (EMT) plays a pivotal role in idiopathic pulmonary fibrosis (IPF). In bleomycin-induced pulmonary fibrosis mice, we observed that inhibition of mTOR (mammalia target of rapamycin) attenuated IPF. Rapamycin suppressed the down-regulation of E-cadherin and up-regulation of fibronectin in bleomycin-induced pulmonary fibrosis mice. In addition, dual immunofluorescence staining for E-cadherin and fibronectin demonstrated that rapamycin pretreatment decreased the proportions of AECs undergoing EMT in bleomycin-induced pulmonary fibrosis, indicating that mTOR inhibition suppressed EMT in vivo...
May 2, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29690905/resolution-of-bleomycin-induced-murine-pulmonary-fibrosis-via-a-splenic-lymphocyte-subpopulation
#18
Koichiro Kamio, Arata Azuma, Kuniko Matsuda, Jiro Usuki, Minoru Inomata, Akemi Morinaga, Takeru Kashiwada, Nobuhiko Nishijima, Shioto Itakura, Nariaki Kokuho, Kenichiro Atsumi, Hiroki Hayashi, Tomoyoshi Yamaguchi, Kazue Fujita, Yoshinobu Saito, Shinji Abe, Kaoru Kubota, Akihiko Gemma
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive disease with high mortality, and the pathogenesis of the disease is still incompletely understood. Although lymphocytes, especially CD4+ CD25+ FoxP3+ regulatory T cells (Tregs), have been implicated in the development of IPF, contradictory results have been reported regarding the contribution of Tregs to fibrosis both in animals and humans. The aim of this study was to investigate whether a specific T cell subset has therapeutic potential in inhibiting bleomycin (BLM)-induced murine pulmonary fibrosis...
April 24, 2018: Respiratory Research
https://www.readbyqxmd.com/read/29681987/buyang-huanwu-decoction-ameliorates-bleomycin-induced-pulmonary-fibrosis-in-rats-via-downregulation-of-related-protein-and-gene-expression
#19
Xuan Wang, Xia Li, Li-Na Wang, Jing-Juan Pan, Xue Yang, Yang-Lin Wei
Little is known about the effects of Buyang Huanwu decoction on pulmonary fibrosis. Herein, 144 healthy SD rats were randomly divided into six groups: blank control group (B), model control group (M), positive medicine control group (Mp), and high-, moderate-, and low-dose Buyang Huanwu decoction groups (Hd, Md, and Ld). A pulmonary fibrosis model was established by endotracheal injection of bleomycin. On the second day of modeling, the corresponding saline, methylprednisolone suspension, and the three doses of Buyang Huanwu decoction were used to treat the 6 groups of rats by intragastric administration for 7, 14, and 28 consecutive days...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29678906/rnai-screening-identifies-a-mechanosensitive-rock-jak2-stat3-network-central-to-myofibroblast-activation
#20
Raymond S Oh, Andrew J Haak, Karry M J Smith, Giovanni Ligresti, Kyoung Moo Choi, Tiao Xie, Shaohua Wang, Paula R Walters, Michael A Thompson, Michelle R Freeman, Logan J Manlove, Vivian M Chu, Carol Feghali-Bostwick, Anja C Roden, Jürgen Schymeinsky, Christina M Pabelick, Y S Prakash, Robert Vassallo, Daniel J Tschumperlin
Myofibroblasts play key roles in wound healing and pathologic fibrosis. Here we undertook an RNAi screen to characterize myofibroblast regulatory genes, using a high-content imaging approach to quantify alpha-smooth muscle actin stress fibers in cultured human fibroblasts. Screen hits were validated on physiological compliance hydrogels, and selected hits tested in primary fibroblasts from patients with idiopathic pulmonary fibrosis. Our RNAi screen led to the identification of STAT3 as an essential mediator of myofibroblast activation and function...
April 20, 2018: Journal of Cell Science
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