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Fibrogenesis

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https://www.readbyqxmd.com/read/28739486/microrna-146a-5p-attenuates-liver-fibrosis-by-suppressing-profibrogenic-effects-of-tgf%C3%AE-1-and-lipopolysaccharide
#1
Yanting Zou, Yu Cai, Di Lu, Yi Zhou, Qunyan Yao, Shuncai Zhang
Liver fibrosis is characterized by proliferation and activation of hepatic stellate cells (HSCs). Transforming growth factor-β1 (TGFβ1) is crucial for liver fibrogenesis, and gut-derived endotoxin (LPS) also plays an important role in liver fibrogenesis. In the present study, we found that microRNA-146a-5p (miR-146a-5p) could regulate TGFβ1/Smad and LPS/NF-κB/Bambi pathways to attenuate liver fibrosis. Downregulated miR-146a-5p and upregulated level of LPS were found in liver of CCl4-treated rats. On cellular level, expression of miR-146a-5p is reduced during primary rat HSCs naturally activation and changed in response to TGFβ1 and/or LPS stimulation in primary rat HSCs and human HSC line LX-2...
July 21, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28729346/distinct-pka-regulatory-subunits-mediate-pge2-inhibition-of-tgf%C3%AE-1-stimulated-collagen-i-translation-and-myofibroblast-differentiation
#2
Scott H Wettlaufer, L Raghu Penke, Katsuhide Okunishi, Marc Peters-Golden
Prostaglandin E2 (PGE2), via cAMP signaling, inhibits a variety of fibroblast functions relevant to fibrogenesis. Among these are their translation of collagen I protein and their differentiation to myofibroblasts. PKA is central to these actions, with cAMP binding to regulatory (R) subunits leading to the release of catalytic subunits. Here we examined the role of specific PKAR subunit isoforms in these inhibitory actions in transforming growth factorβ-1 (TGFβ-1)-stimulated human lung fibroblasts (HLFs)...
July 20, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28720429/stable-isotope-based-flux-studies-in-nonalcoholic-fatty-liver-disease
#3
REVIEW
Arthur McCullough, Stephen Previs, Takhar Kasumov
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is associated with the worldwide epidemics of obesity, diabetes and cardiovascular diseases. NAFLD ranges from benign fat accumulation in the liver (steatosis) to non-alcoholic steatohepatitis (NASH), and cirrhosis which can progress to hepatocellular carcinoma and liver failure. Mass spectrometry and magnetic resonance spectroscopy-coupled stable isotope-based flux studies provide new insights into the understanding of NAFLD pathogenesis and the disease progression...
July 15, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28718381/histological-and-immunohistochemical-characterization-of-the-similarity-and-difference-between-ovarian-endometriomas-and-deep-infiltrating-endometriosis
#4
Xishi Liu, Qi Zhang, Sun-Wei Guo
Ovarian endometrioma (OMA) and deep infiltrating endometriosis (DIE) have long been recognized to have different histology and, as such, postulated to be 2 separate disease entities. Few studies, however, have attempted to elucidate the causes for their differences. Making use of ectopic endometrial tissue samples from 25 and 20 women with OMA and DIE, respectively, and control endometrial tissue samples from 25 women without endometriosis, we conducted an immunohistochemical analysis to evaluate the expression of a group of carefully chosen markers for epithelial-mesenchymal transition (EMT), fibroblast-to-myofibroblast transdifferentiation (FMT), smooth muscle metaplasia (SMM), fibrosis, vascularity, hormonal receptors, and proteins involved in epigenetic modifications...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28709692/ampk-orchestrates-an-elaborate-cascade-protecting-tissue-from-fibrosis-and-aging
#5
REVIEW
Shuai Jiang, Tian Li, Zhi Yang, Wei Yi, Shouyin Di, Yang Sun, Dongjin Wang, Yang Yang
Fibrosis is a common process characterized by excessive extracellular matrix (ECM) accumulation after inflammatory injury, which is also a crucial cause of aging. The process of fibrosis is involved in the pathogenesis of most diseases of the heart, liver, kidney, lung, and other organs/tissues. However, there are no effective therapies for this pathological alteration. Annually, fibrosis represents a huge financial burden for the USA and the world. 5'-AMP-activated protein kinase (AMPK) is a pivotal energy sensor that alleviates or delays the process of fibrogenesis...
July 12, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28707079/down-regulation-of-mir-23a-inhibits-high-glucose-induced-emt-and-renal-fibrogenesis-by-up-regulation-of-snon
#6
Haiping Xu, Fuyun Sun, Xiuli Li, Lina Sun
It has been reported that transforming growth factor-β1 (TGF-β1) signaling plays an important role in the development of diabetic nephropathy (DN). The nuclear transcription co-repressor Ski-related novel protein N (SnoN) is a critical negative regulator of TGF-β1/Smad signal pathway, involving in tubule epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) accumulation, and tubulointerstitial fibrosis. In this study, we focused on miR-23a as a regulator of SnoN. Our purpose is to study the effects of miR-23a on high glucose (HG)-induced EMT process and ECM deposition in HK2 cells...
July 13, 2017: Human Cell
https://www.readbyqxmd.com/read/28705556/supersonic-shear-wave-imaging-of-the-spleen-for-staging-of-liver-fibrosis-in-rats
#7
Xiang-Dong Hu, Hui-Ying Geng, Lei Wang, Hu-Feng Xu, Yuan Su, Si Liang, Lin-Xue Qian
The goal of the work described here was to explore the cause of spleen stiffness (SS) in hepatic fibrogenesis and evaluate the value of SS in liver fibrosis (LF) staging. LF was induced with carbon tetrachloride (CCl4) in rats (n = 40). Supersonic shear wave imaging and contrast-enhanced ultrasound were performed to determine liver stiffness (LS), SS and splenic hemodynamics. SS, LS and free portal pressure exhibited moderate correlations with fibrosis stage (r = 0.744-0.835, p < 0.001). Time-intensity curves of contrast-enhanced ultrasound for the spleen were presented as decreasing peak intensity and slope of decrease, and increasing time to peak...
July 10, 2017: Ultrasound in Medicine & Biology
https://www.readbyqxmd.com/read/28702135/effect-of-tgf-%C3%AE-smad-signaling-pathway-blocking-on-expression-profiles-of-mir-335-mir-150-mir-194-mir-27a-and-mir-199a-of-hepatic-stellate-cells-hscs
#8
Parivash Davoodian, Mehrdad Ravanshad, Seyed Younes Hosseini, Sayyad Khanizadeh, Mohammad Almasian, Azim Nejati Zadeh, Hamed Esmaiili Lashgarian
AIM: The aim of this study was to determine the effect of inhibition of TGF-β/smad signaling on the expression profiles of miR-335, miR-150, miR-194, miR-27a, miR-199a of hepatic stellate cells (HSCs). BACKGROUND: Liver fibrosis is excessive deposition of extracellular matrix proteins due to ongoing inflammation and HSC activation that occurs in most types of chronic liver diseases. Recent studies have shown the importance of microRNAs in the pathogenesis of chronic liver diseases...
2017: Gastroenterology and Hepatology From Bed to Bench
https://www.readbyqxmd.com/read/28701694/defective-cftr-leads-to-aberrant-%C3%AE-catenin-activation-and-kidney-fibrosis
#9
Jie Ting Zhang, Yan Wang, Jun Jiang Chen, Xiao Hu Zhang, Jian Da Dong, Lai Ling Tsang, Xiao Ru Huang, Zhiming Cai, Hui Yao Lan, Xiao Hua Jiang, Hsiao Chang Chan
Cystic fibrosis transmembrane conductance regulator (CFTR), known as a cAMP-activated Cl(-) channel, is widely expressed at the apical membrane of epithelial cells in a wide variety of tissues. Of note, despite the abundant expression of CFTR in mammalian kidney, the role of CFTR in kidney disease development is unclear. Here, we report that CFTR expression is downregulated in the UUO (unilateral ureteral obstruction)-induced kidney fibrosis mouse model and human fibrotic kidneys. Dysfunction or downregulation of CFTR in renal epithelial cells leads to alteration of genes involved in Epithelial-Mesenchymal Transition (EMT) and kidney fibrosis...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28692941/fibroblast-growth-factor-21-ameliorates-high-glucose-induced-fibrogenesis-in-mesangial-cells-through-inhibiting-stat5-signaling-pathway
#10
Shuai Li, Xiaochen Guo, Teng Zhang, Nan Wang, Junyan Li, Pengfei Xu, Shengqi Zhang, Guiping Ren, Deshan Li
Fibroblast growth factor 21 (FGF21) is a member of the FGF family and acts as a potent regulator of glucose and lipid homeostasis, but its effect on renal fibrosis and the underlying mechanisms are totally unknown. The purpose of this study was designed to investigate whether FGF21 has effect on high glucose-induced fibrogenesis in human mesangial cells (HMCs) and the underlying mechanism. High glucose is well known to stimulate the expression of extracelluar matrix (ECM) in human mesangial cells. In humans, overexpression and deposition of ECM lead to renal fibrosis...
July 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28691020/mir-200c-accelerates-hepatic-stellate-cell-induced-liver-fibrosis-via-targeting-the-fog2-pi3k-pathway
#11
Tengfei Ma, Xiuqin Cai, Zifeng Wang, Li Huang, Chang Wang, Songshan Jiang, Yunpeng Hua, Quentin Liu
BACKGROUND: Although expression of miR-200s is aberrant in liver fibrosis, its role in liver fibrogenesis still remains unknown. Here, we investigated the role of miR-200c in the activation of human hepatic stellate cells (HSCs) and induction of liver fibrosis. METHODS: We engineered human HSCs (LX2 cell line) to stably express miR-200c (LX2-200c) or empty vector control (LX2-nc). RESULTS: miR-200c expression upregulated α-smooth muscle actin (SMA) and vimentin, enhanced HSCs growth and migration, increased expression of collagen type I (a main component of ECM) gene and secretion of epidermal growth factor (EGF), and upregulated the phosphorylation of Akt, a downstream effector of the PI3K pathway...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28686848/transcriptional-regulation-of-endmt-in-cardiac-fibrosis-role-of-mrtf-a-and-atf3
#12
Vibhuti Sharma, Nilambra Dogra, Uma Saikia, Madhu Khullar
The etiology of cardiac fibrogenesis is quite diverse but a common feature is the presence of activated fibroblasts. Experimental evidence suggests that a subset of cardiac fibroblasts is derived via transition of vascular endothelial cells into fibroblasts by endothelial to mesenchymal transition (EndMT). During EndMT, endothelial cells lose their endothelial characteristics and acquire a mesenchymal phenotype. Molecular mechanisms and the transcriptional mediators controlling EndMT in heart during development or disease remain relatively undefined...
July 7, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28684188/ascorbate-lacks-significant-influence-in-rats-with-bile-duct-ligation-induced-liver-injury
#13
Hsin-Ling Ho, Teh-Ia Huo, Ting Chang, Wen-Shin Lee, I-Fang Hsin, Fa-Yauh Lee, Hui-Chun Huang, Ming-Chih Hou, Shou-Dong Lee
BACKGROUND: Liver inflammation may induce fibrogenesis, cirrhosis and portal hypertension. Liver cirrhosis is characterized by increased intrahepatic resistance and enhanced vasoconstrictive response. The splanchnic vasodilatation, angiogenesis and portosystemic collaterals formation further bring about lethal complications. Ascorbate is a potent antioxidant with anti-inflammation, anti-fibrosis, and anti-angiogenesis effects. However, the relevant influences in chronic liver injury have not been sufficiently explored...
July 3, 2017: Journal of the Chinese Medical Association: JCMA
https://www.readbyqxmd.com/read/28677860/molecular-magnetic-resonance-imaging-of-lung-fibrogenesis-with-an-oxyamine-based-probe
#14
Philip A Waghorn, Chloe M Jones, Nicholas J Rotile, Steffi K Koerner, Diego S Ferreira, Howard H Chen, Clemens K Probst, Andrew M Tager, Peter Caravan
Fibrogenesis is the active production of extracellular matrix in response to tissue injury. In many chronic diseases persistent fibrogenesis results in the accumulation of scar tissue, which can lead to organ failure and death. However, no non-invasive technique exists to assess this key biological process. All tissue fibrogenesis results in the formation of allysine, which enables collagen cross-linking and leads to tissue stiffening and scar formation. We report herein a novel allysine-binding gadolinium chelate (GdOA), that can non-invasively detect and quantify the extent of fibrogenesis using magnetic resonance imaging (MRI)...
July 5, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28668388/fampk%C3%AE-1-deficiency-suppresses-brown-adipogenesis-in-favor-of-fibrogenesis-during-brown-adipose-tissue-development
#15
Junxing Zhao, Qiyuan Yang, Lupei Zhang, Xingwei Liang, Xiaofei Sun, Bo Wang, Yanting Chen, Meijun Zhu, Min Du
Brown adipose tissue (BAT) dissipates energy for thermogenesis which reduces or prevents obesity and metabolic dysfunction. AMP-activated protein kinase (AMPK) is a master regulator of energy metabolism and its activity is inhibited in the developing BAT due to obesity. We previously found that AMPK is required for brown fat development and thermogenic function, but the non-brown adipogenic differentiation of progenitor cells due to AMPKα1 deficiency has not been defined. We found that, in vivo, the thermogenic capacity and morphology of BAT were compromised due to AMPK deficiency, which was correlated with decreased progenitor density in BAT...
June 28, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28667290/activation-of-hepatic-stellate-cells-by-the-ubiquitin-c-terminal-hydrolase-1-protein-secreted-from-hepatitis-c-virus-infected-hepatocytes
#16
Ju-Chien Cheng, Ching-Ping Tseng, Mei-Huei Liao, Cheng-Yuan Peng, Jau-Song Yu, Po-Heng Chuang, Jing-Tang Huang, Jeremy J W Chen
Hepatitis C virus (HCV) infection of hepatocytes promotes liver fibrosis by activation of hepatic stellate cells (HSCs) and excessive deposition of extracellular matrix in liver tissue. Whether or not host factors released from the HCV-infected hepatocytes play role in HSCs activation is unclear. In this study, HSCs were activated by the conditioned medium derived from HCV replicon cells. Secretomic profiling of HCV replicon cells and the parental Huh7 cells revealed ubiquitin carboxy-terminal hydrolase L1 (UCHL1) as a novel secreted protein from HCV-infected hepatocytes...
June 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28664834/design-of-a-randomised-placebo-controlled-clinical-trial-of-nintedanib-in-patients-with-systemic-sclerosis-associated-interstitial-lung-disease-senscis%C3%A2
#17
Oliver Distler, Kevin K Brown, Jörg H W Distler, Shervin Assassi, Toby M Maher, Vincent Cottin, John Varga, Carl Coeck, Martina Gahlemann, Wiebke Sauter, Hendrik Schmidt, Kristin B Highland
OBJECTIVES: Nintedanib is a tyrosine kinase inhibitor approved for the treatment of idiopathic pulmonary fibrosis (IPF). The pathological pathways involved in fibrogenesis in IPF and interstitial lung disease associated with systemic sclerosis (SSc-ILD) show commonalities; both involve fibroblast activation, myofibroblast accumulation and deposition of extracellular matrix. The SENSCIS™ trial is a randomised, placebo-controlled Phase III trial that will evaluate the efficacy and safety of nintedanib in patients with SSc-ILD (NCT02597933)...
June 29, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28661458/adipokines-in-liver-cirrhosis
#18
REVIEW
Christa Buechler, Elisabeth M Haberl, Lisa Rein-Fischboeck, Charalampos Aslanidis
Liver fibrosis can progress to cirrhosis, which is considered a serious disease. The Child-Pugh score and the model of end-stage liver disease score have been established to assess residual liver function in patients with liver cirrhosis. The development of portal hypertension contributes to ascites, variceal bleeding and further complications in these patients. A transjugular intrahepatic portosystemic shunt (TIPS) is used to lower portal pressure, which represents a major improvement in the treatment of patients...
June 29, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28655415/molecular-signature-of-active-fibrogenesis-prevails-in-biliary-atresia-after-successful-portoenterostomy
#19
Anna Kerola, Hanna Lampela, Jouko Lohi, Päivi Heikkilä, Annika Mutanen, Hannu Jalanko, Mikko P Pakarinen
BACKGROUND: In biliary atresia mechanisms of progressive liver injury leading to need of liver transplantation after successful portoenterostomy remain unknown. A better understanding is a prerequisite for development of novel therapies to extend native liver survival, and we aimed to unravel molecular characteristics of liver injury after successful portoenterostomy. METHODS: Liver biopsies obtained from 28 biliary atresia children during successful portoenterostomy and at median age 3...
June 24, 2017: Surgery
https://www.readbyqxmd.com/read/28652650/role-of-non-steroidal-anti-inflammatory-drugs-on-intestinal-permeability-and-nonalcoholic-fatty-liver-disease
#20
REVIEW
Erika Utzeri, Paolo Usai
The use of non-steroidal anti-inflammatory drugs (NSAIDs) is widespread worldwide thanks to their analgesic, anti-inflammatory and antipyretic effects. However, even more attention is placed upon the recurrence of digestive system complications in the course of their use. Recent data suggests that the complications of the lower gastro-intestinal tract may be as frequent and severe as those of the upper tract. NSAIDs enteropathy is due to enterohepatic recycling of the drugs resulting in a prolonged and repeated exposure of the intestinal mucosa to the compound and its metabolites...
June 14, 2017: World Journal of Gastroenterology: WJG
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