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Lung fibroblast

Liansheng Liu, Jinqiu Lu, Xiaoling Li, Ailing Wu, Qingzhe Wu, Mujun Zhao, Nan Tang, Hai Song
Intracellular transport of membranous organelles and protein complexes to various destinations is fundamental to signaling transduction and cellular function. The cytoplasmic dynein motor and its regulatory proteins LIS1 and NDE1 are required for transporting a variety of cellular cargos along the microtubule network. In this study, we show that deletion of Lis1 in developing lung endoderm and limb mesenchymal cells causes agenesis of the lungs and limbs. In both mutants, there is increased cell death and decreased fibroblast growth factor (FGF) signaling activity...
March 20, 2018: Cell Reports
Kerryn M Taylor, Roxanne Wheeler, Nimisha Singh, Dalene Vosloo, David W Ray, Paula Sommer
Small cell lung cancer (SCLC) is a highly aggressive, predominantly cigarette smoke-induced tumour with poor prognosis. The glucocorticoid receptor (GR), a SCLC tumour suppressor gene, is typically reduced in SCLC. We now show that SCLC cells express high levels of DNA methyltransferase 1 (DNMT1) which accumulates at the GR promoter. DNMT1 expression is further increased by exposure to the tobacco carcinogen NNK. In the untransformed human lung fibroblast cell line, MRC-5, short term NNK treatment decreases GRα mRNA and protein expression due to accumulation of DNMT1 at the GR promoter...
March 20, 2018: Scientific Reports
Ling Chen, Meihui Chen, Zenglei Han, Fengxing Jiang, Chunyuan Xu, Yue Qin, Ning Ding, Yang Liu, Tenglong Zhang, Zhijie An, Chengye Guo
AIMS: We aimed to determine whether cancer-associated fibroblasts (CAFs) are associated with microvessel density (MVD) and lymphatic vessel density (LVD) in lung squamous cell carcinoma, as well as their clinical significance in predicting survival. METHODS: 122 patients were enrolled in the study. Samples were obtained on resection at the Department of Thoracic Surgery of the Qingdao Municipal Hospital between January 2011 and December 2014. Immunohistochemistry was used to determine vessel and lymphatic vessel density, and CAF abundance (fibroblast activation protein α (FAP-α) positivity)...
March 20, 2018: Journal of Clinical Pathology
Kazuhiro J Fujimoto, Daiki Nema, Masayuki Ninomiya, Mamoru Koketsu, Hidetaka Sadanari, Masaya Takemoto, Tohru Daikoku, Tsugiya Murayama
A novel type of antiviral agent for human cytomegalovirus (HCMV) is required, because the appearance of ganciclovir (GCV) resistant viruses has been reported. Tricin (4',5,7-trihydroxy-3',5'-dimethoxyflavone) has been shown to suppress significantly HCMV replication in human embryonic lung (HEL) fibroblast cells. Recently, we revealed that the action of tricin is different from that of GCV and cyclin-dependent kinase 9 (CDK9) is one of the target proteins of tricin. These results suggested that tricin is considered as a novel type of anti-HCMV agent...
March 17, 2018: Antiviral Research
Francesca Andriani, Maria Teresa Majorini, Miguel Mano, Elena Landoni, Rosalba Miceli, Federica Facchinetti, Mavis Mensah, Enrico Fontanella, Matteo Dugo, Mauro Giacca, Ugo Pastorino, Gabriella Sozzi, Domenico Delia, Luca Roz, Daniele Lecis
BACKGROUND: Fibroblasts are crucial mediators of tumor-stroma cross-talk through synthesis and remodeling of the extracellular matrix and production of multiple soluble factors. Nonetheless, little is still known about specific determinants of fibroblast pro-tumorigenic activity in lung cancer. Here, we aimed at understanding the role of miRNAs, which are often altered in stromal cells, in reprogramming fibroblasts towards a tumor-supporting phenotype. METHODS: We employed a co-culture-based high-throughput screening to identify specific miRNAs modulating the pro-tumorigenic potential of lung fibroblasts...
March 20, 2018: Journal of Hematology & Oncology
Alice Pasini, Oliver J Brand, Gisli Jenkins, Alan J Knox, Linhua Pang
Cyclooxygenase-2 (COX-2), with its main antifibrotic metabolite PGE2 , is regarded as an antifibrotic gene. Repressed COX-2 expression and deficient PGE2 have been shown to contribute to the activation of lung fibroblasts and excessive deposition of collagen in pulmonary fibrosis. We have previously demonstrated that COX-2 expression in lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF) is epigenetically silenced and can be restored by epigenetic inhibitors. This study aimed to investigate whether COX-2 downregulation induced by the profibrotic cytokine transforming growth factor-β1 (TGF-β1) in normal lung fibroblasts could be prevented by epigenetic inhibitors...
March 16, 2018: Biochimica et Biophysica Acta
Rong-Quan He, Xia Yang, Liang Liang, Gang Chen, Jie Ma
The present study aimed to explore the potential clinical significance of microRNA (miR)-124-3p expression in the hepatocarcinogenesis and development of hepatocellular carcinoma (HCC), as well as the potential target genes of functional HCC pathways. Reverse transcription-quantitative polymerase chain reaction was performed to evaluate the expression of miR-124-3p in 101 HCC and adjacent non-cancerous tissue samples. Additionally, the association between miR-124-3p expression and clinical parameters was also analyzed...
April 2018: Oncology Letters
Suhailah S Al-Jameel, Tamer E Youssef
Hay synthesis of a novel series of symmetrically tetra-substituted thiophenyl zinc(II)phthalocyanines (RS)4 ZnPcs 4a-c was reported. Their novel 4-thiophenyl-phthalonitriles precursors 3(a-c) were synthesized from their substituted thiophenols 2(a-c). They were screened for their in-vitro antitumor activity on Human lung adenocarcinoma (A549), human breast adenocarcinoma (MCF-7) and hepatocellular carcinoma in comparison with healthy normal cells (human fibroblast cells). Preliminary study of the structure-activity relationship showed that electronic factors in the trifluoromethyl moiety that attached to the ZnPc skeleton had a magnificent effect on the antitumor activity of the newly synthesized (RS)4 ZnPcs 4a-c...
March 17, 2018: World Journal of Microbiology & Biotechnology
Vaideesh Parasaram, Nasim Nosoudi, Aniqa Chowdhury, Naren Vyavahare
mphysema is characterized by degradation of lung alveoli that leads to poor airflow in lungs. Irreversible elastic fiber degradation by matrix metalloproteinases (MMPs) and reactive oxygen species (ROS) activity leads to loss of elasticity and drives the progression of this disease. We investigated if a polyphenol, pentagalloyl glucose (PGG) can increase elastin production in pulmonary fibroblasts. We also studied the effect of PGG treatment in reducing MMP activity and ROS levels in cells. We exposed rat pulmonary fibroblasts to two different types of inflammatory environments i...
March 14, 2018: Biochemical and Biophysical Research Communications
Soyoung Park, Ah-Young Oh, Jung-Hyun Cho, Min-Ho Yoon, Tae-Guen Woo, Somi Kang, Ho-Young Lee, Yunjin Jung, Bum-Joon Park
Quinacrine (QNC), anti-protozoan drug commonly used against Malaria and Giardiasis, has been recently tried for rheumatics and prion diseases via drug repositioning. In addition, several reports suggest anti-tumor effects of QNC through suppression of NF-κB and activation of p53. This study, demonstrates the anti-cancer effect of QNC via a novel pathway through the elimination of check point kinase 1/2 (Chk1/2) under p53 inactivated conditions. Inhibition of p53, by PFT-α or siRNA, promotes QNC-induced apoptosis in normal fibroblast and p53-intact cancer cells...
March 15, 2018: Molecular Cancer Research: MCR
Shencun Fang, Huifang Guo, Yusi Cheng, Zewei Zhou, Wei Zhang, Bing Han, Wei Luo, Jing Wang, Weiping Xie, Jie Chao
Excessive proliferation and migration of fibroblasts contribute to pulmonary fibrosis in silicosis, and both epithelial cells and endothelial cells participate in the accumulation of fibroblasts via the epithelial-mesenchymal transition (EMT) and the endothelial-mesenchymal transition (EndMT), respectively. A mouse endothelial cell line (MML1) was exposed to silicon dioxide (SiO2 , 50 μg/cm2 ), and immunofluorescence and western blot analyses were performed to evaluate levels of specific endothelial and mesenchymal markers and to elucidate the mechanisms by which SiO2 induces the EndMT...
March 14, 2018: Cell Death & Disease
Qianjin Li, Omar Awad Alsaidan, Yongjie Ma, Sungjin Kim, Junchen Liu, Thomas Albers, Kebin Liu, Zanna Beharry, Shaying Zhao, Fen Wang, Iryna Lebedyeva, Houjian Cai
Fibroblast growth factor (FGF)/FGF receptor (FGFR) signaling facilitates tumor initiation and progression. Although currently approved inhibitors of FGFR kinase have shown therapeutic benefit in clinical trials, over-expression or mutations of FGFRs eventually confer drug resistance and thereby abrogate the desired activity of kinase inhibitors in many cancer types. In this study, we report that loss of myristoylation of fibroblast growth factor receptor substrate 2 (FRS2α), a scaffold protein essential for FGFR signaling, inhibits FGF/FGFR-mediated oncogenic signaling and FGF10-induced tumorigenesis...
March 14, 2018: Journal of Biological Chemistry
Federica Camela, Marcella Gallucci, Emanuela di Palmo, Salvatore Cazzato, Mario Lima, Giampaolo Ricci, Andrea Pession
The inflammatory myofibroblastic tumor (IMT) is a rare lesion of unclear etiology and variable clinical course, consisting of a proliferation of fibroblasts and myofibroblasts, mixed with inflammatory cells. Synonyms of IMT are inflammatory pseudotumor and plasma cell granuloma reflecting the alleged inflammatory nature attributed to this lesion, even though this heterogeneity in the disease denomination is probably involved in a dispersion of the literature data. Among primary pulmonary neoplasms, it represents the most frequent endobronchial tumor of childhood and beyond the lung it has been described mainly in the bladder, mediastinum and mesentery...
2018: Frontiers in Pediatrics
Julien Daubriac, Shiwei Han, Jelena Grahovac, Eve Smith, Abdel Hosein, Marguerite Buchanan, Mark Basik, Yves Boucher
Carcinoma-associated fibroblasts (CAFs) can remodel the extracellular matrix to promote cancer cell invasion, but the paracrine signaling between CAFs and cancer cells that regulates tumor cell migration remains to be identified. To determine how the interaction between CAFs and cancer cells modulates the invasiveness of cancer cells, we developed a 3-dimensional co-culture model composed of breast cancer (BC) MDA-MB-231 cell spheroids embedded in a collagen gel with and without CAFs. We found that the crosstalk between CAFs and cancer cells promotes invasion by stimulating the scattering of MDA-MB-231 cells, which was dependent on RhoA/ROCK/phospho MLC signaling in cancer cells but independent of RhoA in CAFs...
February 13, 2018: Oncotarget
Gali Epstein Shochet, Lutz Wollin, David Shitrit
BACKGROUND AND OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with poor prognosis. Activated fibroblasts are the key effector cells in fibrosis, producing excessive amounts of collagen and extracellular matrix (ECM) proteins. Whether the ECM conditioned by IPF fibroblasts determines the phenotype of naïve fibroblasts is difficult to explore. METHODS: IPF-derived primary fibroblasts were cultured on Matrigel and then cleared using ammonium hydroxide, creating an IPF-conditioned matrix (CM)...
March 12, 2018: Respirology: Official Journal of the Asian Pacific Society of Respirology
Seon Min Woo, Seung Un Seo, Kyoung-Jin Min, Taeg Kyu Kwon
BIX-01294 (BIX), a G9a histone methyltransferase inhibitor, has been reported for its anti-proliferative and anticancer activities against various cancer cell lines. In this study, we investigated whether BIX could sensitize TRAIL-mediated apoptosis in various cancer cells. Combined treatment with BIX and TRAIL markedly induced apoptosis in human renal carcinoma (Caki, ACHN, and A498), breast carcinoma (MCF-7), and lung carcinoma (A549) cells. In contrast, BIX and TRAIL co-treatment did not induce apoptosis in normal cells, specifically mouse kidney cell (TCMK-1) and human skin fibroblast (HSF)...
December 2018: Cell Death Discovery
Dong Weng, Jian-Xia Chen, Hao-Hao Li, Feng Liu, Li-Dan Zhou, Hai-Peng Liu, Rui-Juan Zheng, Yan Jiang, Zhong-Hua Liu, Baoxue Ge
The epithelial-mesenchymal transition (EMT) is a multifunctional cell process involved in the pathogenesis of numerous conditions, including fibrosis and cancer. Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease characterized by fibroblast accumulation and collagen deposition in the lungs. The fibroblasts involved in this process partially originate from lung epithelial cells via the EMT. Evidence suggests that the EMT contributes to progression, invasion, and metastasis of various types of cancer...
December 2018: Cell Death Discovery
Gautam Achar, C R Shahini, Siddappa A Patil, Jan Grzegorz Małecki, Szu-Hua Pan, Albert Lan, Xuan-Ren Chen, Srinivasa Budagumpi
In this contribution, a series of sterically-encumbered coumarin substituted benzimidazole-based N-heterocyclic carbene (NHC) precursors (1-12) and their silver(I)-NHC complexes (13-24) are reported. Molecular structure of NHC precursors 8 and 12 and cationic complexes 15 and 16 was established by single crystal X-ray diffraction method. The silver(I) complexes demonstrated various significant intramolecular agostic-like interactions operating between the metal center and the hydrogen atoms of the substituents alongside a variety of feeble π-π stacking interactions...
February 22, 2018: Journal of Inorganic Biochemistry
Ana Valero-Jiménez, Joaquín Zúñiga, José Cisneros, Carina Becerril, Alfonso Salgado, Marco Checa, Ivette Buendía-Roldán, Criselda Mendoza-Milla, Miguel Gaxiola, Annie Pardo, Moisés Selman
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease characterized by epithelial cell activation, expansion of the fibroblast population and excessive extracellular matrix accumulation. The mechanisms are incompletely understood but evidence indicates that the deregulation of several proteases contributes to its pathogenesis. Transmembrane protease serine 4 (TMPRSS4) is a novel type II transmembrane serine protease that may promote migration and facilitate epithelial to mesenchymal transition (EMT), two critical processes in the pathogenesis of IPF...
2018: PloS One
Rachel L Clifford, Nick Fishbane, Jamie Patel, Julia L MacIsaac, Lisa M McEwen, Andrew J Fisher, Corry-Anke Brandsma, Parameswaran Nair, Michael S Kobor, Tillie-Louise Hackett, Alan J Knox
Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease of the lungs that is currently the fourth leading cause of death worldwide. Genetic factors account for only a small amount of COPD risk, but epigenetic mechanisms, including DNA methylation, have the potential to mediate the interactions between an individual's genetics and environmental exposure. DNA methylation is highly cell type-specific, and individual cell type studies of DNA methylation in COPD are sparse...
2018: Clinical Epigenetics
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