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https://www.readbyqxmd.com/read/29677358/lysophosphatidic-acid-induces-ecm-production-via-activation-of-the-mechanosensitive-yap-taz-transcriptional-pathway-in-trabecular-meshwork-cells
#1
Leona T Y Ho, Nikolai Skiba, Christoph Ullmer, Ponugoti Vasantha Rao
Purpose: Lysophosphatidic acid (LPA), a bioactive lipid, has been shown to increase resistance to aqueous humor outflow (AH) through the trabecular meshwork (TM). The molecular basis for this response of the TM to LPA, however, is not completely understood. In this study, we explored the possible involvement of mechanosensitive Yes-associated protein (YAP) and its paralog, transcriptional coactivator with PDZ-binding domain (TAZ), transcriptional activation in extracellular matrix (ECM) production by LPA-induced contractile activity in human TM cells (HTM)...
April 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29677166/in-vitro-identification-of-new-transcriptomic-and-mirnomic-profiles-associated-with-pulmonary-fibrosis-induced-by-high-doses-everolimus-looking-for-new-pathogenetic-markers-and-therapeutic-targets
#2
Simona Granata, Gloria Santoro, Valentina Masola, Paola Tomei, Fabio Sallustio, Paola Pontrelli, Matteo Accetturo, Nadia Antonucci, Pierluigi Carratù, Antonio Lupo, Gianluigi Zaza
The administration of Everolimus (EVE), a mTOR inhibitor used in transplantation and cancer, is often associated with adverse effects including pulmonary fibrosis. Although the underlying mechanism is not fully clarified, this condition could be in part caused by epithelial to mesenchymal transition (EMT) of airway cells. To improve our knowledge, primary bronchial epithelial cells (BE63/3) were treated with EVE (5 and 100 nM) for 24 h. EMT markers (α-SMA, vimentin, fibronectin) were measured by RT-PCR. Transepithelial resistance was measured by Millicell-ERS ohmmeter...
April 20, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29669735/ctgf-vegfa-activated-fibroblasts-promote-tumor-migration-through-micro-environmental-modulation
#3
Wei Wu, Esther A Zaal, Celia R Berkers, Simone Lemeer, Albert J R Heck
Fibroblast activation is associated with tumour progression and implicated in metastasis, but the initial triggering signals required to kick-start this process remain largely unknown. Since small cancerous lesions share limited physical contact with neighboring fibroblasts, we reasoned the first tumour-derived signal for fibroblast activation should be secreted and diffusible. By pulsed metabolic labeling and click-chemistry based affinity enrichment, we sieved through the ductal carcinoma secretome for potential fibroblast activators...
April 18, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29664131/anti-fibrotic-actions-of-ghrelin-by-inhibition-of-the-nadph-oxidase-ros-signaling-pathway
#4
Qian Wang, Xin Sui, Rui Chen, Peiyong Ma, Tao Ding, Dianjun Sui, Ping Yang
This study aims to investigate whether the molecular mechanisms by which Ghrelin inhibits cardiac fibrosis are linked to the NADPH oxidase-ROS signaling pathway. Adult male Sprague Dawley (SD) rats were randomly divided into 4 groups: sham, myocardial infarction (MI), MI + Ghrelin (100 μg/kg, twice daily, subcutaneous for 4 weeks beginning 24 h post-MI), or Ghrelin alone. Adult rat cardiac fibroblasts (CFs) were isolated and pretreated with or without Ghrelin for 24 h, followed by stimulation with or without angiotensin II (Ang II) for another 24 h...
April 17, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29660819/increase-of-ctgf-mrna-expression-by-respiratory-syncytial-virus-infection-is-abrogated-by-caffeine-in-lung-epithelial-cells
#5
Steffen Kunzmann, Christine Krempl, Silvia Seidenspinner, Kirsten Glaser, Christian P Speer, Markus Fehrholz
Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract infection in early childhood. Underlying pathomechanisms of elevated pulmonary morbidity in later infancy are largely unknown. We found that RSV-infected H441 cells showed increased mRNA expression of connective tissue growth factor (CTGF), a key factor in airway remodeling. Additional dexamethasone treatment led to further elevated mRNA levels, indicating additive effects. Caffeine treatment prevented RSV-mediated increase of CTGF mRNA...
April 16, 2018: Influenza and Other Respiratory Viruses
https://www.readbyqxmd.com/read/29660008/exosomal-mir-214-from-endometrial-stromal-cells-inhibits-endometriosis-fibrosis
#6
Di Wu, Pan Lu, Xue Mi, Jinwei Miao
STUDY QUESTION: Is it possible to improve fibrosis in endometriosis by microRNA-214 delivery in exosomes? SUMMARY ANSWER: Upregulation of miR-214 may inhibit fibrogenesis and its delivery by exosomes derived from ectopic endometrial stromal cells, offers an alternative therapeutic approach for endometriosis fibrosis. WHAT IS KNOWN ALREADY: Fibrosis is the primary pathological feature of endometriosis. MiR-214 plays an important role in fibrotic disease...
April 11, 2018: Molecular Human Reproduction
https://www.readbyqxmd.com/read/29644781/inpp4b-overexpression-and-c-kit-downregulation-in-human-achalasia
#7
E Bonora, F Bianco, A Stanzani, F Giancola, A Astolfi, V Indio, C Evangelisti, A M Martelli, E Boschetti, M Lugaresi, A Ioannou, F Torresan, V Stanghellini, P Clavenzani, M Seri, A Moonen, K Van Beek, M Wouters, G E Boeckxstaens, G Zaninotto, S Mattioli, R De Giorgio
BACKGROUND: Achalasia is a rare motility disorder characterized by myenteric neuron and interstitial cells of Cajal (ICC) abnormalities leading to deranged/absent peristalsis and lack of relaxation of the lower esophageal sphincter. The mechanisms contributing to neuronal and ICC changes in achalasia are only partially understood. Our goal was to identify novel molecular features occurring in patients with primary achalasia. METHODS: Esophageal full-thickness biopsies from 42 (22 females; age range: 16-82 years) clinically, radiologically, and manometrically characterized patients with primary achalasia were examined and compared to those obtained from 10 subjects (controls) undergoing surgery for uncomplicated esophageal cancer (or upper stomach disorders)...
April 11, 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/29629343/identification-of-epithelial-mesenchymal-transition-related-target-genes-induced-by-the-mutation-of-smad3-linker-phosphorylation
#8
Sujin Park, Kyung-Min Yang, Yuna Park, Eunji Hong, Chang Pyo Hong, Jinah Park, Kyoungwha Pang, Jihee Lee, Bora Park, Siyoung Lee, Haein An, Mi-Kyung Kwak, Junil Kim, Jin Muk Kang, Pyunggang Kim, Yang Xiao, Guangjun Nie, Akira Ooshima, Seong-Jin Kim
Background: Smad3 linker phosphorylation plays essential roles in tumor progression and metastasis. We have previously reported that the mutation of Smad3 linker phosphorylation sites (Smad3-Erk/Pro-directed kinase site mutant constructs [EPSM]) markedly reduced the tumor progression while increasing the lung metastasis in breast cancer. Methods: We performed high-throughput RNA-Sequencing of the human prostate cancer cell lines infected with adenoviral Smad3-EPSM to identify the genes regulated by Smad3-EPSM...
March 2018: Journal of Cancer Prevention
https://www.readbyqxmd.com/read/29629324/immunohistochemical-analysis-of-the-role-connective-tissue-growth-factor-in-drug-induced-gingival-overgrowth-in-response-to-phenytoin-cyclosporine-and-nifedipine
#9
A J Anand, Sivaram Gopalakrishnan, R Karthikeyan, Debasish Mishra, Shreeyam Mohapatra
Objective: To evaluate for the presence of connective tissue growth factor (CTGF) in drug (phenytoin, cyclosporine, and nifedipine)-induced gingival overgrowth (DIGO) and to compare it with healthy controls in the absence of overgrowth. Materials and Methods: Thirty-five patients were chosen for the study and segregated into study (25) and control groups (10). The study group consisted of phenytoin-induced (10), cyclosporine-induced (10), and nifedipine-induced (5) gingival overgrowth...
January 2018: Journal of International Society of Preventive & Community Dentistry
https://www.readbyqxmd.com/read/29623041/an-adaptogen-withaferin-a-ameliorates-in-vitro-and-in-vivo-pulmonary-fibrosis-by-modulating-the-interplay-of-fibrotic-matricelluar-proteins-and-cytokines
#10
Swarna Bale, Pooladanda Venkatesh, Manoj Sunkoju, Chandraiah Godugu
Pulmonary fibrosis (PF) is chronic lung disease with only two FDA approved clinically available drugs, with limited safety profile. Inadequate therapy motivated us to explore the effect of vimentin inhibitor Withaferin A, as an anti-fibrotic agent against TGF-β1-induced in vitro fibrotic events and Bleomycin induced in vivo fibrosis with an emphasis on epithelial to mesenchymal transition (EMT), extracellular matrix deposition (ECM), inflammation, and angiogenesis. In vitro EMT and fibrotic events were induced by TGF-β1 in alveolar epithelial cells and human fetal lung fibroblasts followed by treatment with Withaferin A (0...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29620147/lncrna-pvt1-promotes-the-angiogenesis-of-vascular-endothelial-cell-by-targeting-mir%C3%A2-26b-to-activate-ctgf-angpt2
#11
Jifu Zheng, Lili Hu, Jing Cheng, Jing Xu, Zhiqiang Zhong, Yuan Yang, Zheng Yuan
Angiogenesis is essential for various biological processes, including tumor blood supply delivery, cancer cell growth, invasion and metastasis. Plasmacytoma variant translocation 1 (PVT1) long noncoding RNA (lncRNA) has been previously reported to affect angiogenesis of glioma microvascular endothelial cells by regulating microRNA (miR)‑186 expression level. However, the specific underlying molecular mechanism of PVT1 regulation of angiogenesis in vascular endothelial cells remains to be elucidated. The present study investigated the role of PVT1 in cell proliferation, migration and vascular tube formation of human umbilical vein endothelial cells (HUVECs) using MTT assay, Transwell migration assay and in vitro vascular tube formation assay, respectively...
March 29, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29618895/buccal-mucosal-epithelial-cells-downregulate-ctgf-expression-in-buccal-submucosal-fibrosis-fibroblasts
#12
Sanjay Gottipamula, Sudarson Sundarrajan, Aditya Moorthy, Sriram Padmanabhan, K N Sridhar
Introduction: Oral submucosal fibrosis (OSMF) is a chronic debilitating fibrotic disease of the oral cavity and is a serious health hazard in south Asia and, increasingly, the rest of the world. The molecular basis behind various treatment modalities to treat OSMF still remains unclear. In this study, we have investigated the in vitro ability of the buccal mucosal cells to reduce the proliferation of the fibroblasts of the fibrotic area in co-culture of cells and also at the molecular levels to reduce the level of connective tissue growth factor (CTGF) in the OSMF fibroblasts (SMF-F)...
June 2018: Journal of Maxillofacial and Oral Surgery
https://www.readbyqxmd.com/read/29605718/a-novel-mouse-model-of-intervertebral-disc-degeneration-shows-altered-cell-fate-and-matrix-homeostasis
#13
Hyowon Choi, Steven Tessier, Elizabeth S Silagi, Rutvin Kyada, Farzad Yousefi, Nancy Pleshko, Irving M Shapiro, Makarand V Risbud
Intervertebral disc degeneration and associated low back and neck pain is a ubiquitous health condition that affects millions of people world-wide, and causes high incidence of disability and enormous medical/societal costs. However, lack of appropriate small animal models with spontaneous disease onset has impeded our ability to understand the pathogenetic mechanisms that characterize and drive the degenerative process. We report, for the first time, early onset spontaneous disc degeneration in SM/J mice known for their poor regenerative capacities compared to "super-healer" LG/J mice...
March 29, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29599817/wenyang-huazhuo-tongluo-formula-inhibits-fibrosis-via-suppressing-wnt-%C3%AE-catenin-signaling-pathway-in-a-bleomycin-induced-systemic-sclerosis-mouse-model
#14
Qian Wang, Wenhua Zang, Li Han, Lei Yang, Songshan Ye, Jingfeng Ouyang, Chaoyun Zhang, Yuefeng Bi, Cuiyue Zhang, Hua Bian
Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs. So far, no Western medicine treatment can completely inhibit or reverse the progress of SSc, while at the same time, our previous series of studies have shown that the treatment of SSc by the Wenyang Huazhuo Tongluo formula (WYHZTL), a Chinese herbal decoction, shows a delightful prospect. The aim of this study is to further investigate the mechanism of anti-fibrosis of WYHZTL formula in SSc mouse model...
2018: Chinese Medicine
https://www.readbyqxmd.com/read/29596890/immuno-modulators-enhance-antigen-specific-immunity-and-anti-tumor-effects-of-mesothelin-specific-chimeric-dna-vaccine-through-promoting-dc-maturation
#15
Yu-Li Chen, Ming-Cheng Chang, Ying-Cheng Chiang, Han-Wei Lin, Nai-Yun Sun, Chi-An Chen, Wei-Zen Sun, Wen-Fang Cheng
As a tumor antigen, mesothelin (MSLN) can be identified in various malignancies. MSLN is potential for antigen-specific cancer vaccines. We generated a novel chimeric DNA vaccine using antigen-specific connective tissue growth factor lined with MSLN (CTGF/MSLN). The anti-tumor effects of the CTGF/MSLN DNA vaccine combined with anti-CD40 Ab and toll-like receptor 3 ligand-poly(I:C) were validated in an MSLN-expressing model. CTGF/MSLN DNA with anti-CD40Ab and poly(I:C) vaccinated mice demonstrated potent anti-tumor effects with longer survival and less tumor volumes...
March 26, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29595072/platycodin-d-reverses-pathological-cardiac-hypertrophy-and-fibrosis-in-spontaneously-hypertensive-rats
#16
Yuan-Chuan Lin, Yu-Chen Lin, Wei-Wen Kuo, Chia-Yao Shen, Yi-Chang Cheng, Yueh-Min Lin, Ruey-Lin Chang, Vijaya V Padma, Chih-Yang Huang, Chih-Yang Huang
Platycodin D (PD) is the main active saponin isolated from Platycodon grandiflorum (PG) and is reported to exhibit anticancer, anti-angiogenic, anti-inflammation and anti-obesity biological effects. The current study aims to evaluate the therapeutic efficacy of PD in cardiac fibrosis and for hypertrophy in spontaneous hypertension rats (SHRs) and to verify inhibition of the signaling pathway. Significant increases in the cardiac functional indices of left ventricular internal diameter end diastole (LVIDd) and left ventricular internal diameter end systole (LVIDs); the eccentric hypertrophy marker p-MEK5; concentric hypertrophy markers, such as CaMKII[Formula: see text] and calcineurin; and expression levels of NFATc3, p-GATA4 and BNP were observed in spontaneously hypertensive groups...
March 29, 2018: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29587800/inhibiting-yap-expression-suppresses-pancreatic-cancer-progression-by-disrupting-tumor-stromal-interactions
#17
Zhengdong Jiang, Cancan Zhou, Liang Cheng, Bin Yan, Ke Chen, Xin Chen, Liang Zong, Jianjun Lei, Wanxing Duan, Qinhong Xu, Xuqi Li, Zheng Wang, Qingyong Ma, Jiguang Ma
BACKGROUND: Hippo/YAP pathway is known to be important for development, growth and organogenesis, and dysregulation of this pathway leads to tumor progression. We and others find that YAP is up-regulated in pancreatic ductal adenocarcinoma (PDAC) and associated with worse prognosis of patients. Activated pancreatic stellate cells (PSCs) forming the components of microenvironment that enhance pancreatic cancer cells (PCs) invasiveness and malignance. However, the role and mechanism of YAP in PDAC tumor-stromal interaction is largely unknown...
March 27, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29575960/connective-tissue-growth-factor-expression-after-angiotensin-ii-exposure-is-dependent-on-transforming-growth-factor-%C3%AE-signaling-via-the-canonical-smad-dependent-pathway-in-hypertensive-induced-myocardial-fibrosis
#18
Chloe Kok Sum Wong, Alec Falkenham, Tanya Myers, Jean-Francois Légaré
INTRODUCTION: Transforming growth factor-β (TGF-β) and connective tissue growth factor (CTGF) are often described as the initial pro-fibrotic mediators upregulated early in fibrosis models dependent on angiotensin II (Ang-II). In the present study, we explore the mechanistic link between TGF-β and CTGF expression by using a novel TGF-β trap. MATERIALS AND METHODS: NIH/3T3 fibroblasts were subjected to TGF-β with or without TGF-β trap or 1D11 antibody, CTGF or CTGF plus TGF-β for six or 24 hours, and then used for quantitative real-time polymerase chain reaction (qRT-PCR) or immunocytochemistry...
January 2018: Journal of the Renin-angiotensin-aldosterone System: JRAAS
https://www.readbyqxmd.com/read/29575527/inhibition-of-yes-associated-protein-suppresses-brain-metastasis-of-human-lung-adenocarcinoma-in-a-murine-model
#19
Ping-Chih Hsu, Jinbai Miao, Zhen Huang, Yi-Lin Yang, Zhidong Xu, Joanna You, Yuyuan Dai, Che-Chung Yeh, Geraldine Chan, Shu Liu, Anatoly Urisman, Cheng-Ta Yang, David M Jablons, Liang You
Yes-associated protein (YAP) is a main mediator of the Hippo pathway and promotes cancer development and progression in human lung cancer. We sought to determine whether inhibition of YAP suppresses metastasis of human lung adenocarcinoma in a murine model. We found that metastatic NSCLC cell lines H2030-BrM3(K-rasG12C mutation) and PC9-BrM3 (EGFRΔexon19 mutation) had a significantly decreased p-YAP(S127)/YAP ratio compared to parental H2030 (K-rasG12C mutation) and PC9 (EGFRΔexon19 mutation) cells (P < ...
March 24, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29574063/connective-tissue-growth-factor-ctgf-from-basics-to-clinics
#20
REVIEW
Yasaman Ramazani, Noël Knops, Mohamed A Elmonem, Tri Q Nguyen, Fanny Oliveira Arcolino, Lambert van den Heuvel, Elena Levtchenko, Dirk Kuypers, Roel Goldschmeding
Connective tissue growth factor, also known as CCN2, is a cysteine-rich matricellular protein involved in the control of biological processes, such as cell proliferation, differentiation, adhesion and angiogenesis, as well as multiple pathologies, such as tumor development and tissue fibrosis. Here, we describe the molecular and biological characteristics of CTGF, its regulation and various functions in the spectrum of development and regeneration to fibrosis. We further outline the preclinical and clinical studies concerning compounds targeting CTGF in various pathologies with the focus on heart, lung, liver, kidney and solid organ transplantation...
March 21, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
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