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primary fibroblasts

Haijun Liu, Shencun Fang, Wei Wang, Yusi Cheng, Yingming Zhang, Hong Liao, Honghong Yao, Jie Chao
BACKGROUND: Silicosis is characterized by accumulation of fibroblasts and excessive deposition of extracellular matrix. Monocyte chemotactic protein-1-induced protein 1 (MCPIP1) plays a critical role in fibrosis induced by SiO2. However, the details of the downstream events of MCPIP1 activity in pulmonary fibrosis remain unclear. To elucidate the role of MCPIP1-induced autophagy in SiO2-induced fibrosis, both the upstream molecular mechanisms and the functional effects of SiO2 on cell apoptosis, proliferation and migration were investigated...
October 25, 2016: Particle and Fibre Toxicology
Zhonghui Guan, Judith Hellman, Mark Schumacher
Tissue injury, whether by trauma, surgical intervention, metabolic dysfunction, ischemia, or infection, evokes a complex cellular response (inflammation) that is associated with painful hyperalgesic states. Although in the acute stages it is necessary for protective reflexes and wound healing, inflammation may persist well beyond the need for tissue repair or survival. Prolonged inflammation may well represent the greatest challenge mammalian organisms face, as it can lead to chronic painful conditions, organ dysfunction, morbidity, and death...
2016: F1000Research
Ratana Lim, Gillian Barker, Stella Liong, Caitlyn Nguyen-Ngo, Stephen Tong, Tu'uhevaha Kaitu'u-Lino, Martha Lappas
INTRODUCTION: Infection and inflammation stimulate pro-inflammatory cytokines, prostaglandins and matrix metalloproteinase (MMP)-9, which play a central role in myometrial contractions and rupture of fetal membranes. In human and mouse immune cells, activating transcription factor 3 (ATF3) is a negative regulator of inflammation. No studies have examined the role of ATF3 in human labour. METHODS: Primary amnion cells were used to determine the effect of interleukin (IL)-1β and the bacterial product fibroblast-stimulating lipopeptide (fsl-1) on ATF3 expression, and the effect of ATF3 siRNA on pro-labour mediators...
November 2016: Placenta
A Villalobos-Hernandez, D Bobbala, R Kandhi, M G M Khan, M Mayhue, C M Dubois, G Ferbeyre, C Saucier, S Ramanathan, S Ilangumaran
BACKGROUND: The suppressor of cytokine signaling 1 (SOCS1) gene is repressed in prostate cancer (PCa) by epigenetic silencing and microRNA miR30d. Increased expression of the SOCS1-targeting miR30d correlates with higher biochemical recurrence, suggesting a tumor suppressor role of SOCS1 in PCa, but the underlying mechanisms are unclear. We have shown that SOCS1 inhibits MET receptor kinase signaling, a key oncogenic pathway in cancer progression. Here we evaluated the role of SOCS1 in attenuating MET signaling in PCa cells and tumor growth in vivo...
October 25, 2016: Prostate Cancer and Prostatic Diseases
Richard Lindqvist, Filip Mundt, Jonathan D Gilthorpe, Silke Wölfel, Nelson O Gekara, Andrea Kröger, Anna K Överby
BACKGROUND: Neurotropic flaviviruses such as tick-borne encephalitis virus (TBEV), Japanese encephalitis virus (JEV), West Nile virus (WNV), and Zika virus (ZIKV) are causative agents of severe brain-related diseases including meningitis, encephalitis, and microcephaly. We have previously shown that local type I interferon response within the central nervous system (CNS) is involved in the protection of mice against tick-borne flavivirus infection. However, the cells responsible for mounting this protective response are not defined...
October 24, 2016: Journal of Neuroinflammation
Ran Xu, Zhen-Zhou Zhang, Lai-Jiang Chen, Hui-Min Yu, Shu-Jie Guo, Ying-Le Xu, Gavin Y Oudit, Yan Zhang, Qing Chang, Bei Song, Dong-Rui Chen, Ding-Liang Zhu, Jiu-Chang Zhong
Apelin has been proved to be a critical mediator of vascular function and homeostasis. Here, we investigated roles of Apelin in aortic remodeling and fibrosis in rats with transverse aortic constriction (TAC). Male Sprague-Dawley rats were subjected to TAC and then randomized to daily deliver Apelin-13 (50μg/kg) or angiotensin type 1 receptor (AT1) blocker Irbesartan (50mg/kg) for 4 weeks. Pressure overload resulted in myocardial hypertrophy, systolic dysfunction, aortic remodeling and adventitial fibrosis with reduced levels of Apelin in ascending aortas of rat after TAC compared with sham-operated group...
October 20, 2016: Peptides
Maria-Cristina Arcangeletti, Rosita Vasile Simone, Isabella Rodighiero, Flora De Conto, Maria-Cristina Medici, Clara Maccari, Carlo Chezzi, Adriana Calderaro
BACKGROUND: Human cytomegalovirus (HCMV) is an opportunistic pathogen leading to severe and even fatal diseases in 'at-risk' categories of individuals upon primary infection or the symptomatic reactivation of the endogenous virus. The mechanisms which make the virus able to reactivate from latency are still matter of intense study. However, the very low number of peripheral blood monocytes (an important latent virus reservoir) harbouring HCMV DNA makes it very difficult to obtain adequate viral quantities to use in such studies...
October 22, 2016: Virology Journal
YanRui Wang, ShaoJie Yue, ZiQiang Luo, ChuanDing Cao, XiaoHe Yu, ZhengChang Liao, MingJie Wang
BACKGROUND: Previous studies have suggested that endogenous glutamate and its N-methyl-D-aspartate receptors (NMDARs) play important roles in hyperoxia-induced acute lung injury in newborn rats. We hypothesized that NMDAR activation also participates in the development of chronic lung injury after withdrawal of hyperoxic conditions. METHODS: In order to rule out the anti-inflammatory effects of NMDAR inhibitor on acute lung injury, the efficacy of MK-801 was evaluated in vivo using newborn Sprague-Dawley rats treated starting 4 days after cessation of hyperoxia exposure (on postnatal day 8)...
October 21, 2016: Respiratory Research
Hongfang Zhang, Conghua Xie, Jing Yue, Zhenzhen Jiang, Rongjing Zhou, Ruifei Xie, Yan Wang, Shixiu Wu
Previous studies on the mechanisms underlying ESCC (esophageal squamous cell carcinoma) chemoresistance only focused on tumor cells while tumor microenvironment has been completely ignored. Our study aimed to clarify the effect of CAFs (cancer-associated fibroblasts), one major component of tumor microenvironment, on the chemoresistance of ESCC. By primary culture, two pairs of CAFs and matched NFs (normal fibroblasts) were isolated from tumor tissues of ESCC patients and matched normal esophageal epithelial tissues, respectively...
October 21, 2016: Molecular Carcinogenesis
Shinnosuke Ikemura, Nao Aramaki, Satoshi Fujii, Keisuke Kirita, Shigeki Umemura, Shingo Matsumoto, Kiyotaka Yoh, Seiji Niho, Hironobu Ohmatsu, Takeshi Kuwata, Motohiro Kojima, Atsushi Ochiai, Tomoko Betsuyaku, Masahiro Tsuboi, Koichi Goto, Genichiro Ishii
Metastasis and growth in neoplastic lesions requires the multi-step regulation of microenvironmental factors. We aimed to elucidate the microenvironmental changes in the process of lymphatic metastasis of lung squamous cell carcinoma. We examined the morphological characteristics of 102 cases of Primary Tumor (PT), 50 of intralymphatic tumor (ILT), 51 of lymph node (LN) micrometastasis (LN-Mic; less than 2 mm in size) and 82 of LN macrometastasis (LN-Mac; greater than 10 mm in size). Afterwards we evaluated the expression of nine molecules (EGFR, FGFR2, CD44, ALDH1, Podoplanin, E-cadherin, S100A4, geminin and ezrin) in matched PT, ILT, LN-Mic and LN-Mac from 23 of these cases...
October 20, 2016: Cancer Science
Emilie Lukasova, Aleš Kovařík, Alena Bačíková, Martin Falk, Stanislav Kozubek
The cellular transition to senescence is associated with extensive chromatin reorganization and gene expression changes. Recent studies appeared implying an association of lamin B1 (LB1) reduction with chromatin rearrangement in human fibroblasts promoted to senescence, while the mechanisms and structural features of these relations were not yet clarified. In this work we examined the functions of LB1 and lamin B receptor (LBR) in human cancer cells. We found that both LB1 and LBR tend to deplete during cancer cells transfer to senescence by γ-irradiation...
October 19, 2016: Biochemical Journal
Ellen Van Damme, Kim Thys, Marianne Tuefferd, Carl Van Hove, Jeroen Aerssens, Marnix Van Loock
Human cytomegalovirus (HCMV) is a betaherpesvirus which rarely presents problems in healthy individuals, yet may result in severe morbidity in immunocompromised patients and in immune-naïve neonates. HCMV has a large 235 kb genome with a coding capacity of at least 165 open reading frames (ORFs). This large genome allows complex gene regulation resulting in different sets of transcripts during lytic and latent infection. While latent virus mainly resides within monocytes and CD34+ progenitor cells, reactivation to lytic infection is driven by differentiation towards terminally differentiated myeloid dendritic cells and macrophages...
2016: PloS One
Nirupama Yalamanchili, Andres Kriete, David Alfego, Kelli M Danowski, Csaba Kari, Ulrich Rodeck
Quiescence is the prevailing state of many cell types under homeostatic conditions. Yet, surprisingly little is known about how quiescent cells respond to energetic and metabolic challenges. To better understand compensatory responses of quiescent cells to metabolic stress, we established, in human primary dermal fibroblasts, an experimental 'energy restriction' model. Quiescence was achieved by short-term culture in serum-deprived media and ATP supply restricted using a combination of glucose transport inhibitors and mitochondrial uncouplers...
2016: Frontiers in Genetics
Ken Takai, Annie Le, Valerie M Weaver, Zena Werb
Increased collagen expression in tumors is associated with increased risk of metastasis, and triple-negative breast cancer (TNBC) has the highest propensity to develop distant metastases when there is evidence of central fibrosis. Transforming growth factor-β (TGF-β) ligands regulated by cancer-associated fibroblasts (CAFs) promote accumulation of fibrosis and cancer progression. In the present study, we have evaluated TNBC tumors with enhanced collagen to determine whether we can reduce metastasis by targeting the CAFs with Pirfenidone (PFD), an anti-fibrotic agent as well as a TGF-β antagonist...
October 14, 2016: Oncotarget
Jeroen Bremer, Olivier Bornert, Alexander Nyström, Antoni Gostynski, Marcel F Jonkman, Annemieke Aartsma-Rus, Peter C van den Akker, Anna Mg Pasmooij
The "generalized severe" form of recessive dystrophic epidermolysis bullosa (RDEB-gen sev) is caused by bi-allelic null mutations in COL7A1, encoding type VII collagen. The absence of type VII collagen leads to blistering of the skin and mucous membranes upon the slightest trauma. Because most patients carry exonic point mutations or small insertions/deletions, most exons of COL7A1 are in-frame, and low levels of type VII collagen already drastically improve the disease phenotype, this gene seems a perfect candidate for antisense oligonucleotide (AON)-mediated exon skipping...
October 18, 2016: Molecular Therapy. Nucleic Acids
Caojian Zuo
OBJECTIVE: Cardiac fibroblasts play a vital role in the progression of fibrotic cardiac remodeling in hypertensive and failing heart. Osteoglycin (OGN) is implicated as a key regulator of left ventricular mass. However, its precise molecular role in cardiac fibrosis remains unknown. This study aims to investigate the impact of OGN in hypertensive cardiac remodeling. DESIGN AND METHOD: OGN deficient mice and its wildtype (WT) littermates were subjected to either angiotensin II (Ang II) infusion or pressure overload induced by transverse aortic constriction (TAC)...
September 2016: Journal of Hypertension
Che Wei Liao, Chi Sheng Hung, Chia Hung Chou, Yen Tin Lin, Xue Ming Wu, Yi Yao Chang, Ying Hsien Chen, Vin Cent Wu, Yi Lwun Ho, Kwan Dun Wu, Yen Hung Lin
OBJECTIVE: Aldosterone induces myocardial fibrosis. The tissue inhibitor of metalloproteinases-1 (TIMP-1) is a key factor of myocardial fibrosis and diastolic dysfunction, but the effect of aldosterone on TIMP-1 expression remains unclear. We tested the hypothesis that aldosterone induces TIMP-1 expression and contributes to the fibrotic process. DESIGN AND METHOD: In the human study, we prospectively enrolled 54 patients with primary aldosteronism. Plasma TIMP-1 and echocardiographic parameters were measured...
September 2016: Journal of Hypertension
Anna V Cherepanova, Zhanna K Nazarkina, Pavel P Laktionov
Oligodeoxynucleotide (ODN) analogues of cell-surface-bound circulating DNA inhibit the dsRNA-induced production of pro-inflammatory interleukin 6, interferon beta and antibacterial peptide beta-defensin 2 not only in human gingival fibroblasts, but also in human primary endothelial and transformed cells (Hela and A431). ODN analogues do not effect dendritic cells activation by poly(I:C). The data obtained indicate that the early stages of the signal transduction cascade are violated by ODN analogues and the effects depend on the cell type...
2016: Advances in Experimental Medicine and Biology
Hung X Nguyen, Robert D Kirkton, Nenad Bursac
The ability to directly enhance electrical excitability of human cells is hampered by the lack of methods to efficiently overexpress large mammalian voltage-gated sodium channels (VGSC). Here we describe the use of small prokaryotic sodium channels (BacNav) to create de novo excitable human tissues and augment impaired action potential conduction in vitro. Lentiviral co-expression of specific BacNav orthologues, an inward-rectifying potassium channel, and connexin-43 in primary human fibroblasts from the heart, skin or brain yields actively conducting cells with customizable electrophysiological phenotypes...
October 18, 2016: Nature Communications
Sandeep Gopal, Hinke A B Multhaupt, Roger Pocock, John R Couchman
Cell-extracellular matrix (ECM) and cell-cell junctions that employ microfilaments are sites of tension. They are important for tissue repair, morphogenetic movements and can be emblematic of matrix contraction in fibrotic disease and the stroma of solid tumors. One cell surface receptor, syndecan-4, has been shown to regulate focal adhesions, junctions that form at the ends of microfilament bundles in response to matrix components such as fibronectin. Recently it has been shown that signaling emanating from this proteoglycan receptor includes regulation of Rho family GTPases and cytosolic calcium...
October 14, 2016: Matrix Biology: Journal of the International Society for Matrix Biology
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