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Proteomics and hepatic fibrosis

Natállia Alle Parreira, Fernando Silva Ramalho, Marlei Josiele Augusto, Deisy Mara Silva, Cibele Maria Prado, Jorge Elias Júnior, Vanderlei Rodrigues, Leandra Náira Zambelli Ramalho
Schistosomiasis mansoni is involved in hepatic fibrogenesis and portal hypertension. Previous studies proved that blockade of some components of the renin-angiotensin system (RAS) reduce liver fibrogenesis. However, the effects of inhibition of early stages of RAS pathway in schistosomal fibrosis have not been studied yet. Thus, the aim of this study was to compare the role of different antihypertensive drugs on hepatic fibrosis in murine schistosomiasis. BALB/c mice (n = 50) weighing 20g were subjected to inoculation of 50 cercariae and submitted to different treatments: aliskiren, 50 mg/kg (n = 10); bradykinin, 2 μg/kg (n = 5); losartan, 10 mg/kg (n = 10); lisinopril 10 mg/kg (n = 5) and control, proportional volume vehicle (n = 5); daily for 14 weeks...
June 8, 2018: Experimental Parasitology
Makan Golizeh, Carlos E Melendez-Pena, Brian J Ward, Sahar Saeed, Cynthia Santamaria, Brian Conway, Curtis Cooper, Marina B Klein, Momar Ndao
BACKGROUND: Hepatic complications of hepatitis C virus (HCV), including fibrosis and cirrhosis are accelerated in human immunodeficiency virus (HIV)-infected individuals. Although, liver biopsy remains the gold standard for staging HCV-associated liver disease, this test can result in serious complications and is subject to sampling errors. These challenges have prompted a search for non-invasive methods for liver fibrosis staging. To this end, we compared serum proteome profiles at different stages of fibrosis in HIV/HCV co- and HCV mono-infected patients using surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF MS)...
2018: PloS One
B Claire McDyre, Mohamed Diwan M AbdulHameed, Matthew G Permenter, William E Dennis, Christine E Baer, Jason M Koontz, Molly H Boyle, Anders Wallqvist, John A Lewis, Danielle L Ippolito
The past decade has seen an increase in the development and clinical use of biomarkers associated with histological features of liver disease. Here, we conduct a comparative histological and global proteomics analysis to identify coregulated modules of proteins in the progression of hepatic steatosis or fibrosis. We orally administered the reference chemicals bromobenzene (BB) or 4,4'-methylenedianiline (4,4'-MDA) to male Sprague-Dawley rats for either 1 single administration or 5 consecutive daily doses. Livers were preserved for histopathology and global proteomics assessment...
February 2018: Toxicologic Pathology
Arianne van Koppen, Lars Verschuren, Anita M van den Hoek, Joanne Verheij, Martine C Morrison, Kelvin Li, Hiroshi Nagabukuro, Adalberto Costessi, Martien P M Caspers, Tim J van den Broek, John Sagartz, Cornelis Kluft, Carine Beysen, Claire Emson, Alain J van Gool, Roel Goldschmeding, Reinout Stoop, Ivana Bobeldijk-Pastorova, Scott M Turner, Guido Hanauer, Roeland Hanemaaijer
Background & Aims: The incidence of nonalcoholic steatohepatitis (NASH) is increasing. The pathophysiological mechanisms of NASH and the sequence of events leading to hepatic fibrosis are incompletely understood. The aim of this study was to gain insight into the dynamics of key molecular processes involved in NASH and to rank early markers for hepatic fibrosis. Methods: A time-course study in low-density lipoprotein-receptor knockout. Leiden mice on a high-fat diet was performed to identify the temporal dynamics of key processes contributing to NASH and fibrosis...
2018: Cellular and Molecular Gastroenterology and Hepatology
Pei-Wen Wang, Yu-Ching Hung, Tung-Ho Wu, Mu-Hong Chen, Chau-Ting Yeh, Tai-Long Pan
Hepatic fibrosis may ultimately result in organ failure and death, a reality compounded by the fact that most drugs for liver fibrosis appear to be effective only if given as a prophylactic or early treatment. In a dimethylnitrosamine-induced liver fibrotic model, aspartate aminotransferase/alanine aminotransferase levels could not precisely distinguish the differences between the initial stage of liver fibrosis and normal control, whereas histological examination indicated that dimethylnitrosamine treatment for two weeks has resulted in hepatic fibrogenesis...
October 24, 2017: Oncotarget
Majid Alhomrani, Jeanne Correia, Marcus Zavou, Bryan Leaw, Nathan Kuk, Rong Xu, Mohamed I Saad, Alexander Hodge, David W Greening, Rebecca Lim, William Sievert
Background: Hepatic stellate cells (HSCs) are the primary collagen-secreting cells in the liver. While HSCs are the major cell type involved in the pathogenesis of liver fibrosis, hepatic macrophages also play an important role in mediating fibrogenesis and fibrosis resolution. Previously, we observed a reduction in HSC activation, proliferation, and collagen synthesis following exposure to human amnion epithelial cells (hAEC) and hAEC-conditioned media (hAEC-CM). This suggested that specific factors secreted by hAEC might be effective in ameliorating liver fibrosis...
2017: Frontiers in Pharmacology
Shu Dong, Fei-Fei Cai, Qi-Long Chen, Ya-Nan Song, Yang Sun, Bin Wei, Xiao-Yan Li, Yi-Yang Hu, Ping Liu, Shi-Bing Su
Liver fibrosis is a consequence of chronic liver disease that can progress to liver cirrhosis or even hepatocarcinoma. Fuzheng Huayu (FZHY), a Chinese herbal formula, has been shown to exert anti-fibrotic effects. To better understand the molecular mechanisms underlying the anti-fibrotic effects of FZHY, we analyzed transcriptomic and proteomic combination profiles in CCl4-induced liver fibrosis in rats, which were treated with extracted FZHY powder (0.35 g/kg/d, ig) for 3 weeks. We showed that FZHY administration significantly improved liver function, alleviated hepatic inflammatory and fibrotic changes, and decreased the hydroxyproline content in the livers of CCl4-treated rats...
November 2, 2017: Acta Pharmacologica Sinica
Lianhong Yin, Yan Qi, Youwei Xu, Lina Xu, Xu Han, Xufeng Tao, Shasha Song, Jinyong Peng
Hepatic stellate cells (HSCs) migration, an important bioprocess, contributes to the development of liver fibrosis. Our previous studies have found the potent activity of dioscin against liver fibrosis by inhibiting HSCs proliferation, triggering the senescence and inducing apoptosis of activated HSCs, but the molecular mechanisms associated with cell migration were not clarified. In this work, iTRAQ (isobaric tags for relative and absolution quantitation)-based quantitative proteomics study was carried out, and a total of 1566 differentially expressed proteins with fold change ≥2...
2017: Frontiers in Pharmacology
Fangming Kan, Lei Ye, Tao Yan, Jiaqi Cao, Jianhua Zheng, Wuping Li
BACKGROUND: Human hepatitis B virus (HBV) infection is an important public health issue in the Asia-Pacific region and is associated with chronic hepatitis, liver fibrosis, cirrhosis and even liver cancer. However, the underlying mechanisms of HBV-associated liver fibrosis remain incompletely understood. RESULTS: In the present study, proteomic and transcriptomic approaches as well as biological network analyses were performed to investigate the differentially expressed molecular signature and key regulatory networks that were associated with HBV-mediated liver fibrosis...
August 22, 2017: BMC Genomics
Kamlesh K Bhopale, Samir M Amer, Lata Kaphalia, Kizhake V Soman, John E Wiktorowicz, Ghulam A Shakeel Ansari, Bhupendra S Kaphalia
BACKGROUND: Chronic alcohol abuse, a major risk factor for such diseases as hepatitis and cirrhosis, impairs hepatic alcohol dehydrogenase (ADH; key ethanol [EtOH]-metabolizing enzyme). Therefore, differentially altered hepatic and plasma proteomes were identified in chronic EtOH feeding model of hepatic ADH-deficient (ADH(-) ) deer mice to understand the metabolic basis of alcoholic liver disease (ALD). METHODS: ADH(-) deer mice were fed 3.5 g% EtOH via Lieber-DeCarli liquid diet daily for 3 months and histology of the liver assessed...
October 2017: Alcoholism, Clinical and Experimental Research
Lina Xu, Lianhong Yin, Xufeng Tao, Yan Qi, Xu Han, Youwei Xu, Shasha Song, Lei Li, Pengyuan Sun, Jinyong Peng
Inhibiting collagen generation is one effective method to treat liver fibrosis. Dioscin showed protective effect against liver fibrosis in our previous studies, and in the present work, SILAC-based proteomics was employed to test the underlying mechanism. A total of 121 differentially expressed proteins caused by dioscin in LX-2 cells were found, and dioscin significantly decreased the expression levels of FN, FAK1, ITGA5, p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR, Col1a1, Col1a2, Col2a1, Col5a1, Col6a1, and increased 2ABB level in vivo and in vitro...
September 2017: Food and Chemical Toxicology
Jibiao Li, Benjamin L Woolbright, Wen Zhao, Yifeng Wang, David Matye, Bruno Hagenbuch, Hartmut Jaeschke, Tiangang Li
Sortilin 1 (Sort1) is an intracellular trafficking receptor that mediates protein sorting in the endocytic or secretory pathways. Recent studies revealed a role of Sort1 in the regulation of cholesterol and bile acid (BA) metabolism. This study further investigated the role of Sort1 in modulating BA detoxification and cholestatic liver injury in bile duct ligated mice. We found that Sort1 knockout (KO) mice had attenuated liver injury 24 h after bile duct ligation (BDL), which was mainly attributed to less bile infarct formation...
January 1, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Hongyu Zhang, Fangyan Chen, Xu Fan, Cong Lin, Yunwei Hao, Handong Wei, Weiran Lin, Ying Jiang, Fuchu He
Understanding the changes of activated HSCs reversion is an essential step toward clarifying the potential roles of HSCs in the treatment of liver fibrosis. In this study, we chose adipocyte differentiation mixture to induce LX-2 cells for 2 days in vitro as reversion phase, comparing with normal cultured LX-2 cells as activation phase. Mass spectrometric-based SILAC technology was adopted to study differentially expressed proteome of LX-2 cells between reversion and activation. Compared with activated HSCs, 273 proteins showed significant differences in reverted HSCs...
March 21, 2017: Scientific Reports
G Craig Wood, Xin Chu, George Argyropoulos, Peter Benotti, David Rolston, Tooraj Mirshahi, Anthony Petrick, John Gabrielson, David J Carey, Johanna K DiStefano, Christopher D Still, Glenn S Gerhard
Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of conditions that include steatohepatitis and fibrosis that are thought to emanate from hepatic steatosis. Few robust biomarkers or diagnostic tests have been developed for hepatic steatosis in the setting of obesity. We have developed a multi-component classifier for hepatic steatosis comprised of phenotypic, genomic, and proteomic variables using data from 576 adults with extreme obesity who underwent bariatric surgery and intra-operative liver biopsy...
March 7, 2017: Scientific Reports
Veronica L Massey, Christine E Dolin, Lauren G Poole, Shanice V Hudson, Deanna L Siow, Guy N Brock, Michael L Merchant, Daniel W Wilkey, Gavin E Arteel
The extracellular matrix (ECM) consists of diverse components that work bidirectionally with surrounding cells to create a responsive microenvironment. In some contexts (e.g., hepatic fibrosis), changes to the ECM are well recognized and understood. However, it is becoming increasingly accepted that the hepatic ECM proteome (i.e., matrisome) responds dynamically to stress well before fibrosis. The term "transitional tissue remodeling" describes qualitative and quantitative ECM changes in response to injury that do not alter the overall architecture of the organ; these changes in ECM may contribute to early disease initiation and/or progression...
March 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Wen Cao, Yan Li, Min Li, Xuerong Zhang, Ming Liao
The anti-fibrotic mechanism of combination therapy with taurine, epigallocatechin gallate and genistein was studied from the perspective of serum proteomics in our previous work. In order to further investigate and systematically analyse other possible therapeutic mechanism of combination therapy against liver fibrosis, isobaric tags for relative and absolute quantification (iTRAQ) proteomic analysis was applied to study the protein profile changes in liver tissue of carbon tetrachloride-induced liver fibrosis rats after combination therapy...
January 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Zeyu Sun, Xiaoli Liu, Jing Jiang, Haijun Huang, Jie Wang, Daxian Wu, Lanjuan Li
We describe a cheap, robust, fast, high-throughput, and flexible proteomic sample processing method based on a regular 96-well plate by acetone precipitation under low centrifuge speed (96PACS), which enables predigestion processing of 96 samples within 2 h. Tested on a complex Huh-7 total lysate, 96PACS produced comparable proteome coverage and even showed better reproducibility than FASP. Quantitative performance of 96PACS was further tested using data-independent acquisition and parallel reaction monitoring quantitation in a set of 6 benchmark samples consisting of 6 serial dilutions of BSA spiked in complex E...
September 6, 2016: Analytical Chemistry
Martina Angi, Helen Kalirai, Samuel Prendergast, Deborah Simpson, Dean E Hammond, Michele C Madigan, Robert J Beynon, Sarah E Coupland
Uveal melanoma (UM), the most common primary intraocular tumour in adults, is characterised by a high frequency of metastases to the liver, typically with a fatal outcome. Proteins secreted from cancer cells ('secretome') are biologically important molecules thought to contribute to tumour progression. We examined the UM secretome by applying a label-free nanoLCMS/MS proteomic approach to profile proteins secreted into culture media by primary UM tumours with a high- (HR; n = 11) or low- (LR; n = 4) metastatic risk, compared to normal choroidal melanocytes (NCM) from unaffected post-mortem eyes...
August 2, 2016: Oncotarget
Santiago Marfà, Manuel Morales-Ruiz, Denise Oró, Jordi Ribera, Guillermo Fernández-Varo, Wladimiro Jiménez
At present, several procedures are used for staging liver fibrosis. However, these methods may involve clinical complications and/or present diagnostic uncertainty mainly in the early stages of the disease. Thus, this study was designed to unveil new non-invasive biomarkers of liver fibrosis in an in vivo model of fibrosis/cirrhosis induction by CCl4 inhalation by using a label-free quantitative LC-MS/MS approach. We analyzed 94 serum samples from adult Wistar rats with different degrees of liver fibrosis and 36 control rats...
2016: Biology Open
Seiichi Tawara, Tomohide Tatsumi, Sadaharu Iio, Ichizou Kobayashi, Minoru Shigekawa, Hayato Hikita, Ryotaro Sakamori, Naoki Hiramatsu, Eiji Miyoshi, Tetsuo Takehara
Fucosylated haptoglobin (Fuc-Hpt) and Mac-2 binding protein (Mac-2 bp) are identified as cancer biomarkers, based on the results from a glyco-proteomic analysis. Recently, we reported that these glyco-biomarkers were associated with liver fibrosis and/or ballooning hepatocytes in patients with nonalcoholic fatty liver disease (NAFLD). We evaluated the ability of these glycoproteins to estimate liver fibrosis in 317 patients with chronic hepatitis C. We measured the serum Fuc-Hpt and Mac-2 bp levels using a lectin-antibody ELISA and ELISA, respectively...
2016: PloS One
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