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TGF-beta AND fibrosis

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https://www.readbyqxmd.com/read/28918914/analysis-of-genomes-and-transcriptomes-of-hepatocellular-carcinomas-identifies-mutations-and-gene-expression-changes-in-the-transforming-growth-factor-beta-pathway-short-title-prognostic-significance-of-tgf-%C3%AE-signature-in-liver-cancer
#1
Jian Chen, Sobia Zaidi, Shuyun Rao, Jiun-Sheng Chen, Liem Phan, Patrizia Farci, Xiaoping Su, Kirti Shetty, Jon White, Fausto Zamboni, Xifeng Wu, Asif Rashid, Nagarajan Pattabiraman, Raja Mazumder, Anelia Horvath, Ray-Chang Wu, Shulin Li, Cuiying Xiao, Chu-Xia Deng, David A Wheeler, Bibhuti Mishra, Rehan Akbani, Lopa Mishra
BACKGROUND & AIMS: Development of hepatocellular carcinoma (HCC) is associated with alterations in the transforming growth factor beta (TGFβ) signaling pathway, which regulates liver inflammation and can have tumor suppressor or promoter activities. Little is known about the roles of specific members of this pathway at specific of HCC development. We took an integrated approach to identify and validate the effects of changes in this pathway in HCC and identify therapeutic targets. METHODS: We performed transcriptome analyses for a total of 488 HCCs that include data from The Cancer Genome Atlas...
September 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28913840/loss-of-regulatory-characteristics-in-cd4-cd25-hi-t-cells-induced-by-impaired-transforming-growth-factor-beta-secretion-in-pneumoconiosis
#2
Lu-Qin Bian, Ling Mao, Ying Bi, Shao-Wei Zhou, Zi-Dan Chen, Jun Wen, Jin Shi, Ling Wang
Pneumoconiosis is caused by the accumulation of airborne dust in the lung, which stimulates a progressive inflammatory response that ultimately results in lung fibrosis and respiratory failure. It is possible that regulatory cells in the immune system could function to suppress inflammation and possibly slow or reverse disease progression. However, results in this study suggest that in pneumoconiosis patients, the regulatory T cells (Tregs) and B cells are functionally impaired. First, we found that pneumoconiosis patients presented an upregulation of CD4(+) CD25(+) T cells compared to controls, whereas the CD4(+) CD25(+) and CD4(+) CD25(hi) T cells were enriched with Th1- and Th17-like cells but not Foxp3-expressing Treg cells and evidenced by significantly higher T-bet, interferon (IFN)-γ, and interleukin (IL)-17 expression but lower Foxp3 and transforming growth factor (TGF)-β expression...
September 15, 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28806736/unravelling-the-interplay-of-sphingolipids-and-tgf-%C3%AE-signaling-in-the-human-corneal-stroma
#3
Sarah E Nicholas, Tyler G Rowsey, Shrestha Priyadarsini, Nawajes A Mandal, Dimitrios Karamichos
PURPOSE: To delineate the role of Sphingolipids (SPLs) in the human cornea and their cross-talks with transforming growth factor beta (TGF-β) in order to develop novel, non-invasive therapies. METHODS: Human corneal fibroblasts (HCFs) were harvested from healthy donors, stimulated with Vitamin C to promote extracellular matrix assembly, treated with exogenous sphingosine-1-phosphate (S1P) or sphingosine kinase inhibitor 2 (SPHK I2) and isolated after 4 weeks for further analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28789951/hepatoprotective-activities-of-rosmarinic-acid-against-extrahepatic-cholestasis-in-rats
#4
Shih-Yi Lin, Ya-Yu Wang, Wen-Ying Chen, Su-Lan Liao, Su-Tze Chou, Ching-Ping Yang, Chun-Jung Chen
Though rosmarinic acid possesses nutritional, pharmaceutical, and toxic properties and shows therapeutic potential on liver diseases, its therapeutic effects against cholestatic liver diseases have not been proven. Using an extrahepatic cholestasis rat model by bile-duct ligation (BDL), daily oral administration of rosmarinic acid showed improvement effects on liver histology, serum biochemicals, ductular reaction, oxidative stress, inflammation, and fibrosis. Rosmarinic acid alleviated BDL-induced transforming growth factor beta-1 (TGF-β1) production and hepatic collagen deposition, and the anti-fibrotic effects were accompanied by reductions in matrix-producing cells and Smad2/3...
August 5, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28752966/-the-study-of-the-effect-and-mechanism-of-glucagon-like-peptide-1-in-bleomycin-induced-pulmonary-fibrosis-in-mice
#5
Mei Liu, Si Gou, Hai-Tao Chen, Zhong-Hua Chen
OBJECTIVE: To investigate the potential value and mechanisms of glucagon like peptide-1 (GLP-1) on bleomycin (BLM)-induced pulmonary fibrosis in mice. METHODS: Mice were treated with a single sublethal dose of BLM (3 mg/kg ) via intratracheal infusion to produce pulmonary fibrosis, and then liraglutide (2 mg/kg) was given to the mice for 28 days by intraperitoneal injection. 28 days after BLM infusion, the number of total cells, macrophages and neutrophils, lymphocytes, and the content of transforming growth factor-beta 1 (TGF-β1) in bronchoalveolar lavage fluid (BALF) were measured...
July 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28744157/the-abc7-regimen-a-new-approach-to-metastatic-breast-cancer-using-seven-common-drugs-to-inhibit-epithelial-to-mesenchymal-transition-and-augment-capecitabine-efficacy
#6
Richard E Kast, Nicolas Skuli, Samuel Cos, Georg Karpel-Massler, Yusuke Shiozawa, Ran Goshen, Marc-Eric Halatsch
Breast cancer metastatic to bone has a poor prognosis despite recent advances in our understanding of the biology of both bone and breast cancer. This article presents a new approach, the ABC7 regimen (Adjuvant for Breast Cancer treatment using seven repurposed drugs), to metastatic breast cancer. ABC7 aims to defeat aspects of epithelial-to-mesenchymal transition (EMT) that lead to dissemination of breast cancer to bone. As add-on to current standard treatment with capecitabine, ABC7 uses ancillary attributes of seven already-marketed noncancer treatment drugs to stop both the natural EMT process inherent to breast cancer and the added EMT occurring as a response to current treatment modalities...
2017: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28696894/preference-of-aerosolized-pirfenidone-to-oral-intake-an-experimental-model-of-pulmonary-fibrosis-by-paraquat
#7
Rokhsana Rasooli, Hamid Rajaian, Abbas Pardakhty, Ali Mandegary
BACKGROUND: Inhalation drug delivery is a fast, effective, and safe route of delivering medication directly to the lungs. Thanks to the large surface area and highly vascularized epithelium in lung, pulmonary drug delivery has been considered as an effective route to deliver drugs to the systemic circulation. Pirfenidone (PF), an oral antifibrotic agent, has been shown to slow down the progression of the lung fibrosis. Inhalation or intrapulmonary delivery of PF appears to be a good alternative to optimize drug delivery and minimize the dosage, adverse and nonspecific effects...
July 11, 2017: Journal of Aerosol Medicine and Pulmonary Drug Delivery
https://www.readbyqxmd.com/read/28659031/gypenosides-ameliorate-carbon-tetrachloride-induced-liver-fibrosis-by-inhibiting-the-differentiation-of-hepatic-progenitor-cells-into-myofibroblasts
#8
Jiamei Chen, Xuewei Li, Yonghong Hu, Wei Liu, Qun Zhou, Hua Zhang, Yongping Mu, Ping Liu
Gypenosides (GPs), the predominant components of Gynostemma pentaphyllum, exert antifibrotic effects; however, the mechanisms underlying their ability to ameliorate liver fibrosis are unclear. Liver fibrosis was induced in C57BL/6 mice via subcutaneous injection of 10% carbon tetrachloride (CCl[Formula: see text] three times a week for two weeks. Then, CCl4 was administered in conjunction with intragastric GPs for another three weeks. For in vitro analyses, WB-F344, hepatatic progenitor cells (HPCs) were treated with transforming growth factor beta 1 (TGF-β1) with or without GPs for 48[Formula: see text]h...
June 28, 2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/28656052/effect-of-huayu-tongluo-herbs-on-reduction-of-proteinuria-via-inhibition-of-wnt-%C3%AE-catenin-signaling-pathway-in-diabetic-rats
#9
Lu Bai, Beibei Huo, Zhiqiang Chen, Qian Guo, Jing Xu, Jing Fang, Jianghua Zhang, Fenfang Zhang
The study investigated the expression of Wnt/β-catenin pathway in diabetic rats and the intervention effect of Huayu Tongluo herbs (HTH). Ten rats were randomly selected as control group and the remaining rats were established as diabetic models. The diabetic rats were randomly divided into model group and HTH treatment group. The intervention was intragastric administration in all rats for 20 weeks. At the end of every 4 weeks, fasting blood glucose and 24 h urinary total protein quantitatively were measured...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28642549/focal-adhesion-kinase-regulates-hepatic-stellate-cell-activation-and-liver-fibrosis
#10
Xue-Ke Zhao, Lei Yu, Ming-Liang Cheng, Pulin Che, Yin-Ying Lu, Quan Zhang, Mao Mu, Hong Li, Li-Li Zhu, Juan-Juan Zhu, Meng Hu, Po Li, Yue-Dong Liang, Xin-Hua Luo, Yi-Ju Cheng, Zhi-Xiang Xu, Qiang Ding
Understanding the underlying molecular mechanisms of liver fibrosis is important to develop effective therapy. Herein, we show that focal-adhesion-kinse (FAK) plays a key role in promoting hepatic stellate cells (HSCs) activation in vitro and liver fibrosis progression in vivo. FAK activation is associated with increased expression of α-smooth muscle actin (α-SMA) and collagen in fibrotic live tissues. Transforming growth factor beta-1 (TGF-β1) induces FAK activation in a time and dose dependent manner. FAK activation precedes the α-SMA expression in HSCs...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28638086/wnt2b-attenuates-hscs-activation-and-liver-fibrosis-through-negative-regulating-tlr4-signaling
#11
Yi Yuan, Qiuju Han, Siyu Li, Zhigang Tian, Jian Zhang
The Wingless-type MMTV integration site family member 2b (Wnt2b) has been found to be a principal mediator of liver development and regeneration. However, the significance of Wnt2b in the pathogenesis of fibrosis-related liver diseases remains undefined. Here, we report that Wnt2b was highly expressed in the fibrotic liver tissues, exhibiting protective effects against activation of hepatic stellate cells (HSCs) and fibrosis progression. We identified a negative regulation of Wnt2b on the toll-like receptor 4 (TLR4) activation-mediated pro-fibrogenic effects...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634911/novel-insights-into-a-reputably-irreversible-process-combined-mrna-and-mirna-profiling-of-tissue-from-vesicourethral-anastomotic-stenosis-after-radical-prostatectomy
#12
T S Worst, K Daskalova, A Steidler, K Berner-Leischner, R Röth, B Niesler, C-A Weis, M C Kriegmair, P Erben, D Pfalzgraf
PURPOSE: Until recently, tissue fibrosis-ultimately leading to permanent scaring-has been considered an irreversible process. However, recent findings indicate that it may be reversible after all. Vesicourethral anastomotic stenosis (VUAS) as fibrous narrowing is a frequent complication after radical prostatectomy with high recurrence rates and requires invasive treatment. The pathophysiology is poorly understood. Therefore, a combined mRNA and miRNA transcription profiling in tissue from VUAS was performed using nCounter technology...
June 20, 2017: World Journal of Urology
https://www.readbyqxmd.com/read/28632033/overexpression-of-alk5-induces-human-tenon-s-capsule-fibroblasts-transdifferentiation-and-fibrosis-in-vitro
#13
Shu-Hao Fu, Hui-Ying Wang, Jia-Ying Zhang, Hui-Min Shi, Nan Zhang, Wen Ye, Yi-Qin Xiao
PURPOSE: To investigate the involvement of activin receptor-like kinase 5 (ALK5) in human Tenon's capsule fibroblasts (HTFs) transdifferentiation and fibrosis. METHODS: (1) Cultured HTFs were treated with transforming growth factor beta 1 (TGF-β1) at different concentrations for different durations, mRNA expression of ALK5 and plasminogen activator inhibitor-1 (PAI-1) was measured by quantitative polymerase chain reaction (PCR) while protein expression of ALK5, α-smooth muscle actin (α-SMA), and extracellular matrix deposition including fibronectin (FN) and collagen I (Col1) was assessed by western blot...
February 28, 2017: Current Eye Research
https://www.readbyqxmd.com/read/28621668/blocking-epithelial-to-mesenchymal-transition-in-glioblastoma-with-a-sextet-of-repurposed-drugs-the-eis-regimen
#14
Richard E Kast, Nicolas Skuli, Georg Karpel-Massler, Guido Frosina, Timothy Ryken, Marc-Eric Halatsch
This paper outlines a treatment protocol to run alongside of standard current treatment of glioblastoma- resection, temozolomide and radiation. The epithelial to mesenchymal transition (EMT) inhibiting sextet, EIS Regimen, uses the ancillary attributes of six older medicines to impede EMT during glioblastoma. EMT is an actively motile, therapy-resisting, low proliferation, transient state that is an integral feature of cancers' lethality generally and of glioblastoma specifically. It is believed to be during the EMT state that glioblastoma's centrifugal migration occurs...
June 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28620270/flucytosine-and-amphotericin-b-coadministration-induces-dose-related-renal-injury
#15
Alexandra Folk, Cornel Balta, Hildegard Herman, Alexandra Ivan, Oana Maria Boldura, Lucian Paiusan, Aurel Ardelean, Anca Hermenean
Invasive fungal infections remain an important clinical problem, and despite recent approaches, they bring high morbidity and mortality. Combination therapies are the most effective; however, adverse effects need to be considered. In this study, we aimed to evaluate the nephrotoxicity induced by combined therapy of flucytosine (FL) and amphotericin B (AMF) at 3 different doses administered to mice for 14 days: 300 μg/kg AMF+50 mg/kg FL; 600 μg/kg AMF+100 mg/kg FL; 900 μg/kg AMF+150 mg/kg FL. Antifungal coadministration triggered nuclear translocation of NF-κB and upregulated nuclear factor kappa-light-chain-enhancer of activated B cells subunit p65 (NF-κB p65) messenger RNA mRNA level in dose-dependent manner...
April 2017: Dose-response: a Publication of International Hormesis Society
https://www.readbyqxmd.com/read/28619646/time-dependent-effects-of-hjp272-an-endothelin-receptor-antagonist-in-bleomycin-induced-pulmonary-fibrosis
#16
Xingjian Liu, Nikhil Khadtare, Hardek Patel, Ralph Stephani, Jerome Cantor
Using a lipopolysaccharide (LPS) model of acute lung injury, we have previously shown that endothelin-1 (ET-1), a potent mediator of vasoconstriction, may act as a "gatekeeper" for the influx of inflammatory cells into the lung. To further investigate the potential of ET-1 to limit the progression of lung injury, hamsters were treated with an endothelin receptor antagonist (ERA), HJP272, either 1 h prior to intratracheal instillation of bleomycin (BLM) or 24 h afterwards. Lung injury and repair were examined by measuring the following parameters: 1) histopathological changes; 2) neutrophil content in bronchoalveolar lavage fluid (BALF); 3) lung collagen content; 4) tumor necrosis factor receptor 1 (TNFR1) expression by BALF macrophages; 5) BALF levels of: a) transforming growth factor beta-1 (TGF-β1), b) stromal cell-derived factor 1 (commonly referred to as CXCL12), and c) platelet-derived growth factor BB (PDGF-BB); 6) alveolar septal cell apoptosis (as measured by the TUNEL assay)...
August 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28600710/the-influence-of-systemic-renin-angiotensin-inhibition-on-ocular-cytokines-related-to-proliferative-vitreoretinopathy
#17
Robert Hoerster, Sascha Fauser, Claus Cursiefen, Bernd Kirchhof, Ludwig M Heindl
PURPOSE: The renin-angiotensin system is involved in the pathogenesis of fibrosis in several organs via induction of transforming growth factor (TGF) beta. In the pathogenesis of proliferative vitreoretinopathy (PVR) TGF-beta plays a pivotal role, promoting transition of retinal pigment epithelial (RPE) cells into myofibroblasts. We studied the influence of angiotensin converting enzyme-inhibition (ACEI) on cytokines and growth factors, related to PVR in aqueous humor. METHODS: We performed a post hoc analysis of a prospectively conducted interventional case series...
June 9, 2017: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/28584818/effects-of-pirfenidone-and-collagen-polyvinylpyrrolidone-on-macroscopic-and-microscopic-changes-tgf-%C3%AE-1-expression-and-collagen-deposition-in-an-experimental-model-of-tracheal-wound-healing
#18
J Raúl Olmos-Zuñiga, Mariana Silva-Martínez, Rogelio Jasso-Victoria, Matilde Baltazares-Lipp, Claudia Hernández-Jiménez, Ivette Buendía-Roldan, Jazmin Jasso-Arenas, Alan Martínez-Salas, Jazmin Calyeca-Gómez, Axel E Guzmán-Cedillo, Miguel Gaxiola-Gaxiola, Laura Romero-Romero
Tracheal stenosis (TS) is a fibrosis originated by prolonged inflammation and increased transforming growth factor beta 1 (TGF-β1) expression and collagen deposition (CD) in the tracheal wound. Several wound-healing modulators (WHMs) have been used to modulate the tracheal healing process and prevent TS, but they have failed, justifying the need to evaluate alternative WHM. The pirfenidone (PFD) and collagen-polyvinylpyrrolidone (Collagen-PVP) decrease inflammation and fibrosis. This study assessed the effect of PFD administration and Collagen-PVP topical application on macroscopic and microscopic changes, TGF-β1 expression, and CD in an experimental model of tracheal wound healing...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28562330/the-correlation-between-pulmonary-fibrosis-and-methylation-of-peripheral-smad3-in-cases-of-pigeon-breeder-s-lung-in-a-chinese-uygur-population
#19
Chao Wu, Wei Ding, Qifeng Li, Wenyi Wang, Mingqin Deng, Rong Jin, Baosen Pang, Xiaohong Yang
Smad3 is a key protein in the transforming growth factor-beta (TGF-β)/Smad signaling pathway, which is involved in fibrosis in many organs. We investigated the relationship between Smad3 gene methylation and pulmonary fibrosis in pigeon breeder's lung (PBL). Twenty Uygur PBL patients with pulmonary fibrosis in Kashi between October 2015 and March 2016 were enrolled. Twenty PBL-free pigeon breeders and 20 healthy non-pigeon breeders enrolled during the same period constituted the negative and normal control groups, respectively...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28561587/protective-effects-of-functional-chicken-liver-hydrolysates-against-liver-fibrogenesis-antioxidation-anti-inflammation-and-antifibrosis
#20
Po-Ju Chen, Jung-Kai Tseng, Yi-Ling Lin, Yi-Hsieng Samuel Wu, Yi-Tse Hsiao, Jr-Wei Chen, Yi-Chen Chen
Via an assay using an Amino Acid Analyzer, pepsin-digested chicken liver hydrolysates (CLHs) contain taurine (365.57 ± 39.04 mg/100 g), carnosine (14.03 ± 1.98 mg/100 g), and anserine (151.58 ± 27.82 mg/100 g). This study aimed to evaluate whether CLHs could alleviate thioacetamide (TAA)-induced fibrosis. A dose of 100 mg TAA/kg BW significantly increased serum liver damage indices and liver cytokine contents. Cell infiltration and monocytes/macrophages in livers of TAA-treated rats were illustrated by the H&E staining and immunohistochemical analysis of cluster of differentiation 68 (CD68, ED1), respectively...
June 21, 2017: Journal of Agricultural and Food Chemistry
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