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https://www.readbyqxmd.com/read/28646679/hypoxia-induced-adam-17-expression-is-mediated-by-rsk1-dependent-c-ebp%C3%AE-activation-in-human-lung-fibroblasts
#1
Jing-Yun Chen, Chien-Huang Lin, Bing-Chang Chen
Hypoxia was identified as a mediator of lung fibrosis in patients with chronic obstructive asthma (COA). Overexpression of a disintegrin and metalloproteinase 17 (ADAM 17) and connective tissue growth factor (CTGF) leads to development of tissue fibrosis. However, the signaling pathway in hypoxia-induced ADAM 17 expression remains poorly defined. In this study, we investigated the roles that ribosomal S-6 kinase 1 (RSK1)/CCAAT/enhancer-binding protein β (C/EBPβ)-dependent ADAM 17 expression plays in hypoxia-induced CTGF expression in human lung fibroblasts...
June 21, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28641514/clinically-relevant-biomarkers-in-acute-heart-failure-an-update
#2
Agnibh Mukherji, Uzair Ansari, Martin Borggrefe, Ibrahim Akin, Michael Behnes
Acute heart failure (AHF) has been one of the fields, where owing to difficulties in diagnosis, prognostic stratification and management the associated morbidity and mortality remains unusually high. The advent of novel biomarkers apart from the traditional B-type natriuretic peptide and N-terminal proBNP involved in myocardial injury, neuro-hormonal activation, and ventricular remodeling augurs immense hope in redefining our approach towards AHF. METHODS: Biomarkers like midregional proatrial natriuretic peptide, soluble ST2, highly-sensitive troponin, and midregional proadrenomedullin are some such examples that have passed various stages of substantiation while there is an array of potential biomarkers in nascent stages like osteopontin, CTGF, GDF-15 and TGF beta-1 awaiting further reiteration...
June 22, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/28629798/proteomic-analysis-of-mesenchymal-to-schwann-cell-transdifferentiation
#3
Anup D Sharma, Jayme Wiederin, Metin Uz, Pawel Ciborowski, Surya K Mallapragada, Howard E Gendelman, Donald S Sakaguchi
While transplantation of Schwann cells facilitates axon regeneration, remyelination and repair after peripheral nerve injury clinical use is limited by cell bioavailability. We posit that such limitation in cell access can be overcome by the use of autologous bone-marrow derived mesenchymal stem cells (MSCs). As MSCs can transdifferentiate to Schwann cell-phenotypes and accelerate nerve regeneration we undertook proteomic evaluation of the cells to uncover the protein contents that affects Schwann cell formulation...
June 16, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28623314/comparative-transcriptomic-and-proteomic-analyses-provide-insights-into-the-key-genes-involved-in-high-altitude-adaptation-in-the-tibetan-pig
#4
Bo Zhang, Yangzom Chamba, Peng Shang, Zhixiu Wang, Jun Ma, Liyuang Wang, Hao Zhang
Tibetan pigs that inhabit the Tibetan Plateau exhibit striking phenotypic and physiological differences from lowland pigs, and have adapted well to extreme conditions. However, the mechanisms involved in regulating gene expression at high altitude in these animals are not fully understood. In this study, we obtained transcriptomic and proteomic data from the heart tissues of Tibetan and Yorkshire pigs raised in the highlands (TH and YH) and lowlands (TL and YL) via RNA-seq and iTRAQ (isobaric tags for relative and absolute quantitation) analyses, respectively...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28617438/connective-tissue-growth-factor-promotes-temozolomide-resistance-in-glioblastoma-through-tgf-%C3%AE-1-dependent-activation-of-smad-erk-signaling
#5
Huijun Zeng, Zhao Yang, Ningbo Xu, Boyang Liu, Zhao Fu, Changlin Lian, Hongbo Guo
Limited benefits and clinical utility of temozolomide (TMZ) for glioblastoma (GB) are frequently compromised by the development of acquired drug resistance. Overcoming TMZ resistance and uncovering the underlying mechanisms are challenges faced during GB chemotherapy. In this study, we reported that connective tissue growth factor (CTGF) was associated with GB chemoresistance and significantly upregulated in TMZ-treated GB cells. CTGF knockdown promoted TMZ-induced cell apoptosis and enhanced chemosensitivity, whereas its overexpression markedly conferred TMZ resistance in vitro and in vivo...
June 15, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28610597/anti-connective-tissue-growth-factor-ctgf-ccn2-monoclonal-antibody-attenuates-skin-fibrosis-in-mice-models-of-systemic-sclerosis
#6
Katsunari Makino, Tomoko Makino, Lukasz Stawski, Kenneth E Lipson, Andrew Leask, Maria Trojanowska
BACKGROUND: Systemic sclerosis (SSc) is characterized by fibrosis of the skin and internal organs. Although the involvement of connective tissue growth factor (CTGF/CCN2) has been well-documented in SSc fibrosis, the therapeutic potential of targeting CTGF in SSc has not been fully investigated. Our aim was to examine the therapeutic potential of CTGF blockade in a preclinical model of SSc using two approaches: smooth muscle cell fibroblast-specific deletion of CTGF (CTGF knockout (KO)) or a human anti-CTGF monoclonal antibody, FG-3019...
June 13, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28605029/the-pancreatic-cancer-microenvironment-a-true-double-agent
#7
REVIEW
Laleh G Melstrom, Marcela D Salazar, Don J Diamond
The tumor microenvironment in pancreatic cancer is a complex balance of pro- and anti-tumor components. The dense desmoplasia consists of immune cells, extracellular matrix, growth factors, cytokines, and cancer associated fibroblasts (CAF) or pancreatic stellate cells (PSC). There are a multitude of targets including hyaluronan, angiogenesis, focal adhesion kinase (FAK), connective tissue growth factor (CTGF), CD40, chemokine (C-X-C motif) receptor 4 (CXCR-4), immunotherapy, and Vitamin D. The developing clinical therapeutics will be reviewed...
June 12, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28591364/roles-of-the-erk1-2-and-pi3k-pkb-signaling-pathways-in-regulating-the-expression-of-extracellular-matrix-genes-in-rat-pulmonary-artery-smooth-muscle-cells
#8
Peng Jia, Yu Hu, Gang Li, Yuqin Sun, Jian Zhao, Jie Fu, Cuixia Lu, Bin Liu
Purpose: To investigate the mechanisms by which PD98059 and LY294002 interfere with the abnormal deposition of extracellular matrix regulated by connective tissue growth factor (CTGF) of rat pulmonary artery smooth muscle cells (PASMCs). Methods: Rat PASMCs were cultured and separated into a control group. Real-time fluorescence quantitative PCR was performed to detect the expression of collagen III and fibronectin mRNA. Immunohistochemistry and western blot analyses were performed to detect the expression of collagen III protein...
May 2017: Acta Cirúrgica Brasileira
https://www.readbyqxmd.com/read/28585302/rictor-mtorc2-promotes-macrophage-activation-and-kidney-fibrosis
#9
Jiafa Ren, Jianzhong Li, Ye Feng, Bingyan Shu, Yuan Gui, Wei Wei, Weichun He, Junwei Yang, Chunsun Dai
Mammalian target of rapamycin (mTOR) signaling controls many essential cellular functions. However, the role for Rictor/mTORC2 in regulating macrophage activation and kidney fibrosis remains largely unknown. We report here that Rictor/mTORC2 was activated in macrophages from the fibrotic kidneys of mice. Ablation of Rictor in macrophages diminished kidney fibrosis, inflammatory cell accumulation, macrophage proliferation and polarization after unilateral ureter obstruction (UUO) or ischemia/reperfusion injury (IRI)...
June 6, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28579882/the-influence-of-connective-tissue-growth-factor-on-rabbit-ligament-injury-repair
#10
Wei Zhang, Junju Zheng, Jiayu Chen, Lipeng Huang
OBJECTIVES: The injured anterior cruciate ligament (ACL) is deemed to exhibit an impaired healing response and attempts at surgical repair have not been successful. Connective tissue growth factor (CTGF) is reported to be associated with wound healing, probably through transforming growth factor beta1 (TGF-β1). METHODS: A rabbit ACL injury model was used to study the effect of CTGF on ligament recovery. Quantitative real-time PCR was performed for detection of changes in RNA levels of TGF-β1, type 1 collagen (COL-I), type 2 collagen (COL-II), SRY-related high mobility group-box gene9 (Sox9), metalloproteinase-1 (TIMP-1) as well as matrix metallopeptidase 13 (MMP-13)...
May 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/28565845/significance-of-new-blood-vessels-in-the-pathogenesis-of-temporomandibular-joint-osteoarthritis
#11
Jianlin Liu, Juan Dai, Yansong Wang, Siyu Lai, Suwen Wang
We studied the significance of new blood vessels in the pathogenesis of temporomandibular joint osteoarthritis (TMJOA). Fifteen 8-week-old female Sprague-Dawley rats were selected to establish TMJOA models of gradually induced occlusal disorders. Five rats were sacrificed at 4, 8 and 16 weeks, and histological exam was conducted along with micro-computed tomography observation on the condyle specimen. The distribution and number of new blood vessels breaking were observed through the tidemark through CD34 immunofluorescence staining...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28562688/smooth-muscle-cell-specific-notch1-haploinsufficiency-restricts-the-progression-of-abdominal-aortic-aneurysm-by-modulating-ctgf-expression
#12
Jaspreet Sachdeva, Advitiya Mahajan, Jeeyun Cheng, Jeremy T Baeten, Brenda Lilly, Helena Kuivaniemi, Chetan P Hans
AIMS: Infiltration of macrophages and apoptosis of vascular smooth muscle cells (VSMCs) promote the development of abdominal aortic aneurysm (AAA). Previously, we demonstrated that global Notch1 deficiency prevents the formation of AAA in a mouse model. Herein, we sought to explore the cell-specific roles of Notch1 in AAA development. METHODS AND RESULTS: Cell-specific Notch1 haploinsufficient mice, generated on Apoe-/- background using Cre-lox technology, were infused with angiotensin II (1000 ng/min/kg) for 28 days...
2017: PloS One
https://www.readbyqxmd.com/read/28562226/inhibition-of-pathological-phenotype-of-hypertrophic-scar-fibroblasts-via-co-culture-with-adipose-derived-stem-cells
#13
Jingcheng Deng, Yuan Shi, Zhen Gao, Wen Jie Zhang, Xiaoli Wu, Weigang Cao, Wei Liu
Hypertrophic scar (HS) is a dermal fibroproliferative disease characterized by fibroblast over-proliferation, overproduction and deposition of the extracellular matrix (ECM). Growing evidence demonstrated that adipose derived stem cells (ASCs) secrete a plethora of trophic and anti-fibrotic factors, which suppress inflammation and ameliorate fibrosis of different tissues. However, few studies investigate their effect on repressing HS activity. This study evaluated the suppressing effect of ASCs on HS fibroblast bioactivity and the possible mechanism via a co-culture model...
May 31, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28546006/atrial-myofibroblast-activation-and-connective-tissue-formation-in-a-porcine-model-of-atrial-fibrillation-and-reduced-left-ventricular-function
#14
Patrick Lugenbiel, Fabian Wenz, Katharina Govorov, Pascal Syren, Hugo A Katus, Dierk Thomas
AIMS: Atrial fibrillation (AF) is associated with fibrosis that slows electrical conduction and causes perpetuation of the arrhythmia. The molecular characterization of AF pathophysiology may provide novel therapeutic options. This study was designed to elucidate profibrotic signaling and myofibroblast activation in a porcine model of atrial tachypacing-induced AF and reduced left ventricular function. MATERIALS AND METHODS: Ten domestic pigs were randomized to sinus rhythm (SR) or AF groups...
July 15, 2017: Life Sciences
https://www.readbyqxmd.com/read/28545716/connective-tissue-growth-factor-regulates-fibrosis-associated-renal-lymphangiogenesis
#15
Hiroshi Kinashi, Lucas L Falke, Tri Q Nguyen, Niels Bovenschen, Jan Aten, Andrew Leask, Yasuhiko Ito, Roel Goldschmeding
Lymphangiogenesis is correlated with the degree of renal interstitial fibrosis. Pro-fibrotic transforming growth factor β induces VEGF-C production, the main driver of lymphangiogenesis. Connective tissue growth factor (CTGF) is an important determinant of fibrotic tissue remodeling, but its possible involvement in lymphangiogenesis has not been explored. We found prominent lymphangiogenesis during tubulointerstitial fibrosis to be associated with increased expression of CTGF and VEGF-C in human obstructed nephropathy as well as in diabetic kidney disease...
May 23, 2017: Kidney International
https://www.readbyqxmd.com/read/28540451/exogenous-cgrp-upregulates-profibrogenic-growth-factors-through-pkc-jnk-signaling-pathway-in-kidney-proximal-tubular-cells
#16
Sang Pil Yoon, Jinu Kim
Kidney denervation prevents the development of tubulointerstitial fibrosis, but the neuropeptide calcitonin gene-related peptide (CGRP) in the denervated kidneys restores the fibrotic feature through the upregulation of profibrogenic growth factors. CGRP is involved in aggravation of inflammation by increasing the number of circulating cells and chemotactic factors. However, it is not clear how CGRP contributes to the upregulation of profibrogenic factors during fibrogenesis. In both human and pig kidney proximal tubular cell lines, administration of 1 nM CGRP significantly increased the levels of transforming growth factor-β1 (TGF-β1) production and connective tissue growth factor (CTGF) expression at 6 and 24 h after the administration...
May 24, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28533328/tendon-stem-progenitor-cells-regulate-inflammation-in-tendon-healing-via-jnk-and-stat3-signaling
#17
Solaiman Tarafder, Esther Chen, Yena Jun, Kristy Kao, Kun Hee Sim, Jungho Back, Francis Y Lee, Chang H Lee
Tendon stem/progenitor cells (TSCs) have been found in different anatomic locations and showed a promising regenerative potential. We identified a role of TSCs in the regulation of inflammation during healing of acute tendon injuries. Delivery of connective tissue growth factor (CTGF) into full-transected rat patellar tendons significantly increased the number of CD146(+) TSCs, leading to enhanced healing. In parallel, CTGF delivery significantly reduced the number of iNOS(+) M1 Mϕs and increased the expression of anti-inflammatory IL-10 at 2 d after surgery, with over 85% CD146(+) TSCs expressing IL-10...
May 22, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28527710/ccn3-regulates-macrophage-foam-cell-formation-and-atherosclerosis
#18
Hong Shi, Chao Zhang, Vinay Pasupuleti, Xingjian Hu, Domenick A Prosdocimo, Wenconghui Wu, Yulan Qing, Shitong Wu, Haneen Mohammad, Stanton L Gerson, Bernard Perbal, Philip A Klenotic, Nianguo Dong, Zhiyong Lin
Recent studies implicate the Cyr61, CTGF, Nov (CCN) matricellular signaling protein family as emerging players in vascular biology, with NOV (alias CCN3) as an important regulator of vascular homeostasis. Herein, we examined the role of CCN3 in the pathogenesis of atherosclerosis. In response to a 15-week high-fat diet feeding, CCN3-deficient mice on the atherosclerosis-prone Apoe(-/-) background developed increased aortic lipid-rich plaques compared to control Apoe(-/-) mice, a result that was observed in the absence of alterations in plasma lipid content...
June 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28520806/als-skeletal-muscle-shows-enhanced-tgf-%C3%AE-signaling-fibrosis-and-induction-of-fibro-adipogenic-progenitor-markers
#19
David Gonzalez, Osvaldo Contreras, Daniela L Rebolledo, Juan Pablo Espinoza, Brigitte van Zundert, Enrique Brandan
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in which upper and lower motoneurons degenerate leading to muscle wasting, paralysis and eventually death from respiratory failure. Several studies indicate that skeletal muscle contributes to disease progression; however the molecular mechanisms remain elusive. Fibrosis is a common feature in skeletal muscle under chronic damage conditions such as those caused by muscular dystrophies or denervation. However, the exact mechanisms of fibrosis induction and the cellular bases of this pathological response are unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28512636/expression-of-yap-taz-in-keratocystic-odontogenic-tumors-and-its-possible-association-with-proliferative-behavior
#20
Qi-Wen Man, Yan-Qi Ma, Jin-Yuan Liu, Yi Zhao, Bing Liu, Yi-Fang Zhao
The aim of this study is to clarify whether YAP/TAZ is involved in the pathogenesis and proliferative growth of keratocystic odontogenic tumor (KCOT). The expression levels of YAP/TAZ and downstream proteins and genes in normal oral mucosa (OM) and KCOT were determined and compared by immunohistochemistry and real-time quantitative PCR. The results showed that the expression of YAP/TAZ and downstream proteins (Cyr61, CTGF) was significantly upregulated in KCOT with upregulation of Ki-67 compared to OM. Importantly, the mRNA levels of transcription factors (TEAD1, TEAD4, and RUNX2) and cell cycle related genes (CDK2, PCNA), which interact with the transcriptional coactivators YAP/TAZ, are also upregulated in the KCOT...
2017: BioMed Research International
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