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https://www.readbyqxmd.com/read/28341659/chronic-microaspiration-of-bile-acids-induces-lung-fibrosis-through-multiple-mechanisms-in-rats
#1
Bi Chen, Wen Jie You, Xue Qing Liu, Shan Xue, Hui Qin, Han Dong Jiang
Gastroesophageal reflux (GER) and microaspiration of duodenogastric refluxate have been recognized as a risk factor for pulmonary fibrosis. Recent evidence implicates that bile acid microaspiration may contribute to the development of lung fibrosis. However, the molecular evidences are scarce and the underlying mechanisms remain to be elucidated. We have recently demonstrated that bile acids induce activation of alveolar epithelial cells and lung fibroblasts in vitro In this study, a rat model of bile acid microaspiration was established by weekly intratracheal instillation of three major bile acids including chenodeoxycholic acid (CDCA), deoxycholic acid (DCA) and lithocholic acid (LCA) ...
March 24, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28339034/the-sirt1-activator-srt1720-attenuates-renal-fibrosis-by-inhibiting-ctgf-and-oxidative-stress
#2
Yunzhuo Ren, Chunyang Du, Yonghong Shi, Jingying Wei, Haijiang Wu, Huixian Cui
The transforming growth factor-β1 (TGF-β1)/connective tissue growth factor (CTGF) pathway plays an important role in the pathogenesis and progression of chronic kidney disease. Oxidative stress is also involved in TGF-β1 signalling. Sirtuin 1 (Sirt1) exerts a number of pleiotropic effects, protecting against renal disease, including inhibiting fibrosis and oxidative metabolism. In this study, we investigated the role of the Sirt1 activator, SRT1720, in unilateral ureteral obstruction (UUO)-induced tubulointerstitial fibrosis and aimed to determine whether this role depends on the inhibition of oxidative stress and the TGF-β1/CTGF pathway...
March 22, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28337873/cyclosporine%C3%A2-a-augments-endoplasmic-reticulum-stress-markers-and-expression-of-matrix-protein-mrna
#3
S R Rao, R Subbarayan, D M Girija
Cyclosporine-A induces gingival overgrowth with disturbance in the homeostasis of cells and connective tissue proteins. Human gingival fibroblasts were cultured with cyclosporine A, and the expression of two vital endoplasmic stress markers and two prime matrix proteins (connective tissue growth factor (CTGF and periostin) were assessed by RT-PCR. We found that expression of Glucose-Regulated Protein 78 (GRP78/BIP) and CCAAT/enhancer binding protein, C/EBP homologous protein (CHOP) were significantly increased, along with CTGF and periostin, suggesting a role for these factors in gingival overgrowth...
January 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28334711/quantitative-proteomics-analysis-of-ischemia-reperfusion-injury-modulated-proteins-in-cardiac-microvascular-endothelial-cells-and-the-protective-role-of-tongxinluo
#4
Qing Li, He-He Cui, Yue-Jin Yang, Xiang-Dong Li, Gui-Hao Chen, Xia-Qiu Tian, Chen Jin, Qiu-Ting Dong, Pei-Sen Huang, Jun Xu
BACKGROUND: The protection of endothelial cells (ECs) against reperfusion injury has received little attention. In this study, we used Tandem Mass Tag (TMT) labeling proteomics to investigate the modulated proteins in an in vitro model of cardiac microvascular endothelial cells (CMECs) subjected to ischemia/reperfusion (I/R) injury and their alteration by traditional Chinese medicine Tongxinluo (TXL). METHODS: Human CMECs were subjected to 2 h of hypoxia followed by 2 h of reoxygenation with different concentrations of TXL Protein expression profiles of CMECs were determined using tandem mass spectrometry...
March 24, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28332553/mir-18a-counteracts-akt-and-erk-activation-to-inhibit-the-proliferation-of-pancreatic-progenitor-cells
#5
Xuyan Li, Zhenwu Zhang, Yunchao Li, Yicheng Zhao, Wenjun Zhai, Lin Yang, Delin Kong, Chunyan Wu, Zhenbao Chen, Chun-Bo Teng
Activation of endogenous stem/progenitor cells to repair injured tissues is an ideal option for disease treatment. However, adult pancreatic progenitor cells remain in a quiescent state in vivo. Thus, it is difficult to stimulate proliferation and differentiation in these progenitor cells, and the cause remains elusive. miR-17-92 cluster miRNAs are highly conserved in mammals and are expressed in multiple tissue stem/progenitor cells, but their role in pancreatic progenitor cells are less well known. In the present study, we demonstrate that miR-18a, but not the other members of the miR-17-92 gene cluster, inhibits the proliferation of pancreatic progenitor cells in vitro and ex vivo...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28331224/enhanced-wnt-signalling-in-hepatocytes-is-associated-with-schistosoma-japonicum-infection-and-contributes-to-liver-fibrosis
#6
Qi Wang, Xin Chou, Fei Guan, Zhengming Fang, Shengjun Lu, Jiahui Lei, Yonglong Li, Wenqi Liu
Liver fibrosis is the most serious pathology caused by Schistosoma japonicum infection, which arises when schistosome eggs are deposited in the liver. Eosinophils, macrophages and hepatic stellate cells (HSCs) have been identified as major cellular contributors to the development of granulomas and fibrosis, but little is known about the effects of hepatocytes on granuloma formation. Here, we found that the levels of Wnt signalling-related molecules, transforming growth factor β (TGF-β) and connective tissue growth factor (CTGF) in hepatocytes were markedly elevated after S...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28330503/caffeine-modulates-glucocorticoid-induced-expression-of-ctgf-in-lung-epithelial-cells-and-fibroblasts
#7
Markus Fehrholz, Kirsten Glaser, Christian P Speer, Silvia Seidenspinner, Barbara Ottensmeier, Steffen Kunzmann
BACKGROUND: Although caffeine and glucocorticoids are frequently used to treat chronic lung disease in preterm neonates, potential interactions are largely unknown. While anti-inflammatory effects of glucocorticoids are well defined, their impact on airway remodeling is less characterized. Caffeine has been ascribed to positive effects on airway inflammation as well as remodeling. Connective tissue growth factor (CTGF, CCN2) plays a key role in airway remodeling and has been implicated in the pathogenesis of chronic lung diseases such as bronchopulmonary dysplasia (BPD) in preterm infants...
March 23, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28325283/silencing-of-carbohydrate-sulfotransferase-15-hinders-murine-pulmonary-fibrosis-development
#8
Yoshiro Kai, Koichi Tomoda, Hiroyuki Yoneyama, Masahiro Kitabatake, Atsuhiro Nakamura, Toshihiro Ito, Masanori Yoshikawa, Hiroshi Kimura
Pulmonary fibrosis is a progressive lung disorder characterized by interstitial fibrosis, for which no effective treatments are available. Chondroitin sulfate proteoglycan (CSPG) has been shown to be a mediator, but the specific component of glycosaminoglycan chains of CSPG has not been explored. We show that chondroitin sulfate E-type (CS-E) is involved in fibrogenesis. Small interfering RNA (siRNA) targeting carbohydrate sulfotransferase 15 (CHST15) was designed to inhibit CHST15 mRNA and its product, CS-E...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28323847/role-of-the-mapks-tgf-%C3%AE-1-traf6-signaling-pathway-in-postoperative-atrial-fibrillation
#9
Daoliang Zhang, Xiaoqing Chen, Qian Wang, Shaohui Wu, Yue Zheng, Xu Liu
OBJECTIVES: To explore the relationship between the MAPKs/TGF-β1/TRAF6 signaling pathway and atrial fibrosis in patients with rheumatic heart disease (RHD) and its role in atrial fibrillation (AF) after cardiac surgery on the basis of our previous animal study of the MAPKs/TGF-β1/TRAF6 signaling pathway in atrial fibrosis. METHODS: A total of 57 patients with RHD without a history of AF consented to left atrial biopsy. Histopathology quantified the percentage of fibrosis, and real-time PCR and western blot assessed the mRNA and protein expression of TGF-β1, TRAF6, and connective tissue growth factor (CTGF), respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28323698/hypertrophy-and-fibrosis-of-the-ligamentum-flavum-in-lumbar-spinal-stenosis-is-associated-with-increased-expression-of-lpa-and-lpar1
#10
Kai Zhang, Wei Sun, Xin-Yu Liu, Chang-Qing Zhao, Hua Li, Xiao-Jiang Sun, Xie You-Zhuan, Wei Ding, Jie Zhao
STUDY DESIGN: Histologic, immunohistochemical (IHC), and enzyme-linked immunosorbent assay analysis of the human ligamentum flavum (LF). OBJECTIVE: The purpose of this study was to determine the level of expression of lysophosphatidic acid (LPA) in the LF from lumbar spinal stenosis (LSS) patients and to analyze the relationship among LPA, LPA receptors (LPARs), and LF hypertrophy. SUMMARY OF BACKGROUND DATA: LF hypertrophy and fibrosis are important causes of LSS...
April 2017: Clinical Spine Surgery
https://www.readbyqxmd.com/read/28320972/sensing-relative-signal-in-the-tgf-%C3%AE-smad-pathway
#11
Christopher L Frick, Clare Yarka, Harry Nunns, Lea Goentoro
How signaling pathways function reliably despite cellular variation remains a question in many systems. In the transforming growth factor-β (Tgf-β) pathway, exposure to ligand stimulates nuclear localization of Smad proteins, which then regulate target gene expression. Examining Smad3 dynamics in live reporter cells, we found evidence for fold-change detection. Although the level of nuclear Smad3 varied across cells, the fold change in the level of nuclear Smad3 was a more precise outcome of ligand stimulation...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28320863/rac1-gtpase-regulates-11%C3%AE-hydroxysteroid-dehydrogenase-type-2-and-fibrotic-remodeling
#12
Daniel Lavall, Pia Schuster, Nadine Jacobs, Andrey Kazakov, Michael Böhm, Ulrich Laufs
The aim of the study was to characterize the role of Rac1 GTPase for the mineralocorticoid receptor (MR) mediated pro-fibrotic remodeling. Transgenic mice with cardiac overexpression of constitutively active Rac1 (RacET) develop an age-dependent phenotype with atrial dilatation, fibrosis and atrial fibrillation. Expression of MR was similar in RacET and wild-type (WT) mice. The expression of 11β hydroxysteroid dehydrogenase type 2 (11β-HSD2) was age-dependently upregulated in the atria and the left ventricles of RacET mice on mRNA and protein level...
March 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28314802/an-ex-vivo-model-to-induce-early-fibrosis-like-changes-in-human-precision-cut-lung-slices
#13
Hani N Alsafadi, Claudia A Staab-Weijnitz, Mareike Lehmann, Michael Lindner, Britta Peschel, Melanie Königshoff, Darcy Elizabeth Wagner
IPF is a devastating chronic interstitial lung disease (ILD) characterized by lung tissue scarring and high morbidity. Lung epithelial injury, myofibroblast activation, and deranged repair are believed to be key processes involved in disease onset and progression but the exact molecular mechanisms behind IPF remain unclear. Several drugs have been shown to slow disease progression, but treatments which halt or reverse IPF progression have not been identified. Ex vivo models of human lung have been proposed for drug discovery, one of which is precision-cut lung slices (PCLS)...
March 17, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28294324/blocking-fibrotic-signaling-in-fibroblasts-from-patients-with-carpal-tunnel-syndrome
#14
REVIEW
Yoshiaki Yamanaka, Anne Gingery, Gosuke Oki, Tai-Hua Yang, Chunfeng Zhao, Peter C Amadio
Fibrosis of the subsynovial connective tissue (SSCT) in carpal tunnel syndrome (CTS) patients is increasingly recognized as an important aspect of CTS pathophysiology. In this study, we evaluated the effect of blocking profibrotic pathways in fibroblasts from the SSCT in CTS patients. Fibroblasts were stimulated with transforming growth factor β1 (TGF-β1), and then treated either with a specific fibrosis pathway inhibitor targeting TGF-β receptor type 1 (TβRI), platelet-derived growth factor receptor (PDGFR), epidermal growth factor receptor (EGFR) or vascular endothelial growth factor receptor (VEGFR)...
March 10, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28289072/downregulation-of-mir-15a-b-accelerates-fibrotic-remodelling-in-the-type-2-diabetic-human-and-mouse-heart
#15
Shruti Rawal, Pujika Emani Munasinghe, Prashanth Thevakar, Jason Kar Sheng Lew, Gregory T Jones, Michael Ja Willams, Philip Davis, Richard W Bunton, Ivor F Galvin, Patrick Manning, Regis R Lamberts, Rajesh G Katare
AIM: Myocardial fibrosis is a well established cause of increased myocardial stiffness and subsequent diastolic dysfunction in the diabetic heart. The molecular regulators that drive the process of fibrotic events in the diabetic heart are still unknown. We determined the role of the microRNA (miR)-15 family in fibrotic remodelling of the diabetic heart. METHODS AND RESULTS: Right atrial appendage (RAA) and left ventricular (LV) biopsy tissues collected from diabetic and non-diabetic patients undergoing coronary artery bypass graft surgery showed significant downregulation of miR-15a and -15b...
March 13, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28287886/overexpressed-connective-tissue-growth-factor-in-cardiomyocytes-attenuates-left-ventricular-remodeling-induced-by-angiotensin-ii-perfusion
#16
Ying Zhang, Hua Yan, Gong-Chang Guang, Zheng-Rong Deng
To evaluate the improving effects of specifically overexpressed connective tissue growth factor (CTGF) in cardiomyocytes on mice with hypertension induced by angiotensin II (AngII) perfusion, 24 transgenic mice with cardiac-restricted overexpression of CTGF (Tg-CTGF) were divided into two equal groups that were perfused with acetic acid and AngII, respectively, for 7 days. Another 24 cage-control wild-type C57BL/6 mice (NLC) were divided and treated identically. Blood pressure was detected by caudal artery cannulation...
2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/28277128/expression-of-cyclooxygenase-1-and-cyclooxygenase-2-syndecan-1-and-connective-tissue-growth-factor-in-benign-and-malignant-breast-tissue-from-premenopausal-women
#17
M Fahlén, H Zhang, L Löfgren, B Masironi, E von Schoultz, B von Schoultz, L Sahlin
Stromal factors have been identified as important for tumorigenesis and metastases of breast cancer. From 49 premenopausal women, samples were collected from benign or malignant tumors and the seemingly normal tissue adjacent to the tumor. The factors studied, with real-time polymerase chain reaction (PCR) and immunohistochemistry, were cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2), syndecan-1 (S-1) and connective tissue growth factor (CTGF). COX-1 and S-1 mRNA levels were higher in the malignant tumors than in normal and benign tissues...
February 21, 2017: Gynecological Endocrinology
https://www.readbyqxmd.com/read/28275008/pparg-is-central-to-the-initiation-and-propagation-of-human-angiomyolipoma-suggesting-its-potential-as-a-therapeutic-target
#18
Oren Pleniceanu, Racheli Shukrun, Dorit Omer, Einav Vax, Itamar Kanter, Klaudyna Dziedzic, Naomi Pode-Shakked, Michal Mark-Daniei, Sara Pri-Chen, Yehudit Gnatek, Hadas Alfandary, Nira Varda-Bloom, Dekel D Bar-Lev, Naomi Bollag, Rachel Shtainfeld, Leah Armon, Achia Urbach, Tomer Kalisky, Arnon Nagler, Orit Harari-Steinberg, Jack L Arbiser, Benjamin Dekel
Angiomyolipoma (AML), the most common benign renal tumor, can result in severe morbidity from hemorrhage and renal failure. While mTORC1 activation is involved in its growth, mTORC1 inhibitors fail to eradicate AML, highlighting the need for new therapies. Moreover, the identity of the AML cell of origin is obscure. AML research, however, is hampered by the lack of in vivo models. Here, we establish a human AML-xenograft (Xn) model in mice, recapitulating AML at the histological and molecular levels. Microarray analysis demonstrated tumor growth in vivo to involve robust PPARG-pathway activation...
March 8, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28273641/betulinic-acid-attenuates-renal-fibrosis-in-rat-chronic-kidney-disease-model
#19
Anshuk Sharma, Richa Thakur, Madhu C Lingaraju, Dhirendra Kumar, Karikalan Mathesh, Avinash G Telang, Thakur Uttam Singh, Dinesh Kumar
BACKGROUND: Most chronic kidney diseases (CKDs), regardless of the nature of the initial injury, progress to end-stage renal disease (ESRD) characterized by fibrosis with irreversible loss of tissue and function. Thus, improved and more effective therapies are critical. Betulinic acid (BA), a pentacyclic triterpene is a compound in the pipeline of anti-cancer drug development. It has been shown to a possess variety of beneficial effects in many disease conditions. However, its efficacy against CKD is yet to be explored...
March 5, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28272698/effect-of-mir-203-expression-on-myocardial-fibrosis
#20
Q He, C-M Wang, J-Y Qin, Y-J Zhang, D-S Xia, X Chen, S-Z Guo, X-D Zhao, Q-Y Guo, C-Z Lu
OBJECTIVE: Cardiovascular disease is one of the diseases threatening human health. Myocardial fibrosis is a major cause of cardiovascular diseases. Studies have shown that over expression of miR-203 can inhibit the fibrosis. Therefore, in this study, the effect of differential expression of miR-203 on fibrosis of cultured mouse cardiomyocytes was investigated. MATERIALS AND METHODS: Activators and inhibitors of miR-203 were designed according to the sequence of miR-203, synthesized, and transfected into mouse cardiomyocytes to establish activator group, inhibitor group, and control group...
February 2017: European Review for Medical and Pharmacological Sciences
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