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Bleomycin pulmonary fibrosis

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https://www.readbyqxmd.com/read/29140132/mediation-of-the-single-walled-carbon-nanotubes-induced-pulmonary-fibrogenic-response-by-osteopontin-and-tgf-%C3%AE-1
#1
Timur O Khaliullin, Elena R Kisin, Ashley R Murray, Naveena Yanamala, Michael R Shurin, Dmitriy W Gutkin, Liliya M Fatkhutdinova, Valerian E Kagan, Anna A Shvedova
PURPOSE OF THE STUDY: A number of in vivo studies have shown that pulmonary exposure to carbon nanotubes (CNTs) may lead to an acute local inflammatory response, pulmonary fibrosis, and granulomatous lesions. Among the factors that play direct roles in initiation and progression of fibrotic processes are epithelial-mesenchymal transition and myofibroblasts recruitment/differentiation, both mediated by transforming growth factor-β1 (TGF-β1). Yet, other contributors to TGF-β1 associated signaling, such as osteopontin (OPN) has not been fully investigated...
October 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/29138212/bax-inhibiting-peptide-attenuates-bleomycin-induced-lung-injury-in-mice
#2
Kunihiro Suzuki, Toyoshi Yanagihara, Tetsuya Yokoyama, Takashige Maeyama, Saiko Ogata-Suetsugu, Masako Arimura-Omori, Hironori Mikumo, Naoki Hamada, Eiji Harada, Kazuyoshi Kuwano, Taishi Harada, Yoichi Nakanishi
Rationale: Bax is a pro-apoptotic member of the Bcl-2 family of proteins, and plays a central role in mitochondria-dependent apoptosis. Several lines of evidence have implied that Bax is involved in both epithelial apoptosis and fibroblast proliferation in idiopathic pulmonary fibrosis; however, the mechanisms remain unknown. Bax-inhibiting peptide V5 (BIP-V5) exhibits membrane permeability and inhibits the activation of Bax.Objective: The purpose of this study was to investigate whether the control of Bax activity by BIP-V5 reduces the degree of bleomycin-induced lung injury...
November 14, 2017: Biology Open
https://www.readbyqxmd.com/read/29131071/highly-selective-endothelin-1-receptor-a-inhibition-prevents-bleomycin-induced-pulmonary-inflammation-and-fibrosis-in-mice
#3
Nikolaos Manitsopoulos, Ioanna Nikitopoulou, Nikolaos A Maniatis, Christina Magkou, Anastasia Kotanidou, Stylianos E Orfanos
BACKGROUND: Pulmonary fibrosis is a chronic disease, which progressively leads to respiratory failure and ultimately death. Endothelin-1 (ET-1), a vasoconstrictor secreted by endothelial cells, promotes vasoconstriction by activation of its receptors A and B. OBJECTIVES: We addressed the role of highly selective ET-1 receptor A (ETA) inhibition in the pathogenesis of experimental pulmonary fibrosis by bleomycin (BLM). METHODS: BLM sulfate (2 U/mL) or saline was intratracheally administered to C57/Bl6 mice (4 groups; n = 5-11/group)...
November 9, 2017: Respiration; International Review of Thoracic Diseases
https://www.readbyqxmd.com/read/29129520/f2-isoprostanes-can-mediate-bleomycin-induced-lung-fibrosis
#4
Beatrice Arezzini, Daniela Vecchio, Cinzia Signorini, Blerta Stringa, Concetta Gardi
F2-isoprostanes (F2-IsoPs) have been considered markers of oxidative stress in various pulmonary diseases, but little is known about their possible role in pulmonary fibrosis. In this study, we have investigated the potential key role of F2-IsoPs as markers and mediators of bleomycin (BLM)-induced pulmonary fibrosis in rats. During the in vivo study, plasma F2-IsoPs showed a peak at 7 days and remained elevated for the entire experimental period. Lung F2-IsoP content nearly tripled 7 days following the intratracheal instillation of BLM, and by 28 days, the value increased about fivefold compared to the controls...
November 9, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29122847/human-airway-trypsin-like-protease-exerts-potent-antifibrotic-action-in-pulmonary-fibrosis
#5
Awen Menou, Pauline Flajolet, JanWillem Duitman, Aurélien Justet, Sophie Moog, Madeleine Jaillet, Laure Tabèze, Brigitte Solhonne, Marc Garnier, Hervé Mal, Pierre Mordant, Yves Castier, Aurélie Cazes, Jean-Michel Sallenave, Arnaud A Mailleux, Bruno Crestani
Idiopathic pulmonary fibrosis (IPF) is characterized by the deposition of excessive extracellular matrix and the destruction of lung parenchyma, resulting from an aberrant wound-healing response. Although IPF is often associated with an imbalance in protease activity, the mechanisms underlying the sustained repair mechanisms are not fully understood. Here, we addressed the role of the recently identified, membrane-anchored serine protease human airway trypsin-like protease (HAT). In the present study, we show that both HAT expression and activity were up-regulated in human IPF specimens...
November 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29118928/mir-5100-targets-tob2-to-drive-epithelial-mesenchymal-transition-associated-with-activating-smad2-3-in-lung-epithelial-cells
#6
Chun-Yan Li, Ya-Hong Wang, Zi-Ying Lin, La-Wei Yang, Sheng-Lan Gao, Tie Liu, Bao-An Zou, Zhan-Chun Pan, Ze-Qing Song, Gang Liu
Idiopathic pulmonary fibrosis (IPF) is a devastating disease and the pathogenesis of IPF remains unclear. Our previous study indicated that miR-5100 promotes the proliferation and metastasis of lung epithelial cells. In this study, we investigated the effect and mechanism of miR-5100 on bleomycin (BLM)-induced mouse lung fibrosis and transforming growth factor β (TGF-β1) or epidermal growth factor (EGF) induced EMT-model in A549 and Beas-2B cells. The elevated level of miR-5100 was observed in both the mouse lung fibrosis tissues and EMT cell model...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29118902/inhibitory-effects-of-thalidomide-on-bleomycin-induced-pulmonary-fibrosis-in-rats-via-regulation-of-thioredoxin-reductase-and-inflammations
#7
Xiaoying Dong, Xin Li, Minghui Li, Ming Chen, Qian Fan, Wei Wei
In this study, the potential clinical effects of thalidomide on bleomycin-induced pulmonary fibrosis were investigated. A Sprague-Dawley rats' model of pulmonary fibrosis induced by an intratracheal instillation of bleomycin was adopted. The rats in thalidomide treated groups were intraperitoneally injected with thalidomide (10, 20, 50 mg/kg) daily for 28 days, while the rats in control and bleomycin treated groups were injected with a saline solution. The effects of thalidomide on pulmonary injury were evaluated by the lung wet/dry weight ratios, cell counts, and histopathological examination...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29118338/sialidase-inhibitors-attenuate-pulmonary-fibrosis-in-a-mouse-model
#8
Tejas R Karhadkar, Darrell Pilling, Nehemiah Cox, Richard H Gomer
Fibrosis involves increasing amounts of scar tissue appearing in a tissue, but what drives this is unclear. In fibrotic lesions in human and mouse lungs, we found extensive desialylation of glycoconjugates, and upregulation of sialidases. The fibrosis-associated cytokine TGF-β1 upregulates sialidases in human airway epithelium cells, lung fibroblasts, and immune system cells. Conversely, addition of sialidases to human peripheral blood mononuclear cells induces accumulation of extracellular TGF-β1, forming what appears to be a sialidase - TGF-β1 - sialidase positive feedback loop...
November 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29115860/lysyl-oxidase-like-1-protein-deficiency-protects-mice-from-adtgf-%C3%AE-1-induced-pulmonary-fibrosis
#9
Pierre-Simon Bellaye, Chiko Shimbori, Chandak Upagupta, Seidai Sato, Wei Shi, Jack Gauldie, Kjetil Ask, Martin Kolb
Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterised by excessive deposition of extracellular matrix (ECM) in the lung parenchyma. The abnormal ECM deposition slowly overtakes normal lung tissue disturbing gas-exchange and leading to respiratory failure and death. ECM cross-linking and subsequent stiffening is thought to be a major contributor of disease progression and also promotes the activation of TGF-β1, one of the main pro-fibrotic growth factors. Lysyl oxidase-like1 (LOXL1) belongs to the crosslinking enzyme family and has been shown to be upregulated in active fibrotic regions of bleomycin-treated mice and IPF patients...
November 8, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29115383/induced-pluripotent-stem-cell-conditioned-medium-suppresses-pulmonary-fibroblast-to-myofibroblast-differentiation-via-the-inhibition-of-tgf-%C3%AE-1-smad-pathway
#10
Yan Zhou, Qiang Zhang, Yuan Gao, Mingqi Tan, Rui Zheng, Li Zhao, Xiaoye Zhang
Therapeutic strategies based on stem cells have been shown to have potential in improving the condition of severe lung diseases. In this study, the suppressive effects of conditioned medium (CM) of induced pluripotent stem cells (iPSCs) on pulmonary fibroblast differentiation were investigated in a series of in vitro and in vivo experiments. Moreover, the underlying mechanisms through which iPSC-CM inhibited the differentiation of fibroblasts into myofibroblasts were explored as well. iPSCs were generated using a mouse 3-gene transfection method, myofibroblast-like cells were induced by incubating human fibroblasts with transforming growth factor-β1 (TGF-β1) and mouse models of pulmonary fibrosis (PF) were established by an injection of bleomycin...
October 19, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29113323/reduced-expression-of-bmp3-contributes-to-the-development-of-pulmonary-fibrosis-and-predicts-the-unfavorable-prognosis-in-iip-patients
#11
Xiaoting Yu, Pan Gu, Ziling Huang, Xia Fang, Ying Jiang, Qun Luo, Xia Li, Xuyou Zhu, Mengna Zhan, Junbang Wang, Lichao Fan, Rongchang Chen, Juehua Yu, Yingying Gu, Aibin Liang, Xianghua Yi
Idiopathic pulmonary fibrosis (IPF) and idiopathic nonspecific interstitial pneumonia (INSIP) are two related diseases involving varying degrees of pulmonary fibrosis with no effective cure. Bone morphogenetic protein 3 (BMP3) is a member of the transforming growth factor-β (TGF-β) super-family, which has not been implicated in pulmonary fibrosis previously. In this study, we aimed to investigate the potential role of BMP3 playing in pulmonary fibrosis from clinical diagnosis to molecular signaling regulation...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29097816/anti-inflammatory-and-anti-fibrotic-effects-of-intravenous-adipose-derived-stem-cell-transplantation-in-a-mouse-model-of-bleomycin-induced-interstitial-pneumonia
#12
Takuya Kotani, Ryota Masutani, Takayasu Suzuka, Katsuhiro Oda, Shigeki Makino, Masaaki Ii
Adipose-derived stem cells (AdSCs) have recently been considered a useful treatment tool for autoimmune disease because of their anti-inflammatory and immunosuppressive effects. We investigated the therapeutic effect of intravenous AdSC transplantation in a mouse model of bleomycin-induced lung injury. AdSCs accumulated in the pulmonary interstitium and inhibited both inflammation and fibrosis in the lung, markedly improving the survival rate of mice with bleomycin-induced lung injury in a cell number-dependent manner...
November 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29079731/involvement-of-er-stress-pi3k-akt-activation-and-lung-fibroblast-proliferation-in-bleomycin-induced-pulmonary-fibrosis
#13
Han-Shui Hsu, Chen-Chi Liu, Jiun-Han Lin, Tien-Wei Hsu, Jyuan-Wei Hsu, Kelly Su, Shih-Chieh Hung
Pulmonary fibrosis is characterized by fibroblast proliferation and extracellular matrix remodelling, leading to respiratory insufficiency. The mechanisms underlying this progressive and devastating disease remain unclear. Conditions that can impair the function of the endoplasmic reticulum (ER) cause accumulation of unfolded or misfolded proteins, resulting in ER stress and activation of the unfolded protein response (UPR). ER stress has been implicated in many conditions including cancer, diabetes, obesity, and inflammation...
October 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29079188/klf2-attenuates-bleomycin-induced-pulmonary-fibrosis-and-inflammation-with-regulation-of-ap-1
#14
Jian Shi, Li-Rong Zhou, Xiao-Sheng Wang, Jun-Feng Du, Ming-Ming Jiang, Zhan Song, Guang-Chao Han, Zhi-Tao Mai
Pulmonary fibrosis (PF) is a chronic, fibrosing interstitial pneumonia and devastating disease. Here we investigated the potential roles of Kruppel-like factor 2 (KLF2) on pulmonary fibrosis and inflammation response. A mouse model of pulmonary fibrosis was established by intratracheal injection of bleomycin (BLM). The mRNA and protein levels of KLF2 were assayed by RT-PCR and Western blotting respectively. The extent of lung fibrosis was determined using hematoxylin and eosin (HE) staining and Masson's trichrome staining, and the hydroxyproline content was quantified...
October 24, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29067109/tiam1-inhibits-lung-fibroblast-differentiation-in-pulmonary-fibrosis
#15
Zhicheng Huang, Shuangyan Sun, Changliang Yang, Jun Zheng, Yingji Nan, Ruikun Zhao, Zhiguo Lang, Hang Li, Lixia Ma
The differentiation of fibroblasts to myofibroblasts is critical for the development of idiopathic pulmonary fibrosis (IPF). T-cell lymphoma invasion and metastasis 1 (TIAM1) is known to be associated with amyotrophic lateral sclerosis 1 and colorectal cancer; however, its role in IPF is unclear. The aim of the present study was to investigate the expression and roles of TIAM1 in lung fibroblasts during pulmonary fibrosis. It was demonstrated that TIAM1 expression was significantly increased in fibrotic lung tissue and lung fibroblasts from bleomycin (BLM)-treated mice compared with control mice (P<0...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29061768/cutting-edge-anti-tim-3-treatment-exacerbates-pulmonary-inflammation-and-fibrosis-in-mice
#16
Takuma Isshiki, Hisaya Akiba, Masafumi Nakayama, Norihiro Harada, Ko Okumura, Sakae Homma, Sachiko Miyake
Promising results of immune checkpoint inhibitors have indicated the use of immunotherapy against malignant tumors. However, they cause serious side effects, including autoimmune diseases and pneumonitis. T cell Ig and mucin domain (TIM)-3 is a new candidate immune checkpoint molecule; however, the potential toxicity associated with anti-TIM-3 treatment is unknown. In this study, we investigated the pathological contribution of anti-TIM-3 mAb in a bleomycin-induced lung inflammation and fibrosis model. Anti-TIM-3-treated mice showed more severe inflammation and peribronchiolar fibrosis compared with control IgG-treated mice...
October 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29055573/bleomycin-electrosclerotherapy-new-treatment-to-manage-vascular-malformations
#17
L McMorrow, M Shaikh, G Kessell, T Muir
Venous malformations are congenital anomalies of the vascular system. The injection of bleomycin (a cytotoxic, antitumour drug) into the lesion is a safe and effective treatment for low-flow (venous and lymphatic) malformations, but its use systemically has been associated with pulmonary fibrosis. Intralesional injection of bleomycin is considered to have a lower risk, but caution should be used when planning treatment, with particular regard to respiratory function. Electroporation is the temporary application of an electrical field across a tissue to increase (briefly) the permeability of the cell membrane in that tissue...
November 2017: British Journal of Oral & Maxillofacial Surgery
https://www.readbyqxmd.com/read/29053339/ecm-crosslinking-enhances-fibroblast-growth-and-protects-against-matrix-proteolysis-in-lung-fibrosis
#18
Christopher J Philp, Ivonne Siebeke, Debbie Clements, Suzanne Miller, Anthony Habgood, Alison E John, Vidya Navaratnam, Richard B Hubbard, Gisli Jenkins, Simon R Johnson
Idiopathic pulmonary fibrosis (IPF) is characterised by accumulation of extra cellular matrix (ECM) proteins and fibroblast proliferation. ECM cross-linking enzymes have been implicated in fibrotic diseases and we hypothesised that the ECM in IPF is abnormally cross-linked which enhances fibroblast growth and resistance to normal ECM turnover. We used a combination of in vitro ECM preparations and in vivo assays to examine the expression of cross-linking enzymes and the effect of their inhibitors on fibroblast growth and ECM turnover...
October 20, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29050340/nogo-b-promotes-emt-in-lung-fibrosis-via-mmp14-mediates-free-tgf-beta1-formation
#19
Ye Xiong, Jing Zhang, Lingzhi Shi, Yunye Ning, Ying Zhu, Si Chen, Meng Yang, Jingyu Chen, Guo-Wu Zhou, Qiang Li
Idiopathic pulmonary fibrosis (IPF) is a lung disease with an extremely poor prognosis. Epithelial mesenchymal transition (EMT) appearing on the airway epithelial cell plays an essential role in the formation and development of Idiopathic pulmonary fibrosis. In this paper, Bleomycin (BLM)-induced mice model combined with bioinformatics analysis were employed to elucidate the potential mechanism of EMT in pulmonary fibrosis. The obtained results showed that endoplasmic reticulum protein Nogo-b may promote MMP14-mediated proprotein maturation of TGF-β1, accelerating the release of free TGF-β1 in type II airway epithelial cells A549, subsquently, induce the epithelial-mesenchymal transition (EMT) of the cell...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29045477/tubastatin-ameliorates-pulmonary-fibrosis-by-targeting-the-tgf%C3%AE-pi3k-akt-pathway
#20
Shigeki Saito, Yan Zhuang, Bin Shan, Svitlana Danchuk, Fayong Luo, Martina Korfei, Andreas Guenther, Joseph A Lasky
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal disease. Histone deacetylase 6 (HDAC6) alters function and fate of various proteins via deacetylation of lysine residues, and is implicated in TGF-β1-induced EMT (epithelial-mesenchymal transition). However, the role of HDAC6 in pulmonary fibrosis is unknown. METHODS: HDAC6 expression in IPF and control lungs was assessed by quantitative real-time PCR (qRT-PCR) and immunoblots. Lung fibroblasts were treated with TGF-β1 ± HDAC6 inhibitors (Tubacin, Tubastatin, ACY1215, or MC1568), and fibrotic markers such as type I collagen were assessed using qRT-PCR and immunoblots...
2017: PloS One
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