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Hepatic stellate cells

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https://www.readbyqxmd.com/read/28544786/mir-122-modification-enhances-the-therapeutic-efficacy-of-adipose-tissue-derived-mesenchymal-stem-cells-against-liver-fibrosis
#1
Guohua Lou, Ying Yang, Feifei Liu, Bingjue Ye, Zhi Chen, Min Zheng, Yanning Liu
Mesenchymal stem cell (MSC) transplantation alone may be insufficient for treatment of liver fibrosis because of complicated histopathological changes in the liver. Given that miR-122 plays an essential role in liver fibrosis by negatively regulating the proliferation and transactivation of hepatic stellate cells (HSCs), this study investigated whether miR-122 modification can improve the therapeutic efficacy of adipose tissue-derived MSCs in treating liver fibrosis. MiR-122-modified AMSCs (AMSC-122) were constructed through lentivirus-mediated transfer of pre-miR-122...
May 24, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28540429/identification-of-markers-for-quiescent-pancreatic-stellate-cells-in-the-normal-human-pancreas
#2
Michael Friberg Bruun Nielsen, Michael Bau Mortensen, Sönke Detlefsen
Pancreatic stellate cells (PSCs) play a central role as source of fibrogenic cells in pancreatic cancer and chronic pancreatitis. In contrast to quiescent hepatic stellate cells (qHSCs), a specific marker for quiescent PSCs (qPSCs) that can be used in formalin-fixed and paraffin embedded (FFPE) normal human pancreatic tissue has not been identified. The aim of this study was to identify a marker enabling the identification of qPSCs in normal human FFPE pancreatic tissue. Immunohistochemical (IHC), double-IHC, immunofluorescence (IF) and double-IF analyses were carried out using a tissue microarray consisting of cores with normal human pancreatic tissue...
May 25, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28539891/double-knockdown-of-phd1-and-keap1-attenuated-hypoxia-induced-injuries-in-hepatocytes
#3
Jing Liu, Yiping Li, Lei Liu, Zhi Wang, Chuanbing Shi, Zhengyuan Cheng, Xiaoyi Zhang, Fengan Ding, Ping Sheng Chen
Background and Aims: Hypoxia and oxidative stress contribute toward liver fibrosis. In this experiment, we used small hairpin RNA (shRNA) to interfere with the intracellular oxygen sensor-prolyl hydroxylase 1 (PHD1) and the intracellular oxidative stress sensor-kelch-like ECH associated protein 1 (Keap1) in the hypoxic hepatocytes in order to investigate the function of PHD1and Keap1. Methods: We first established the CCl4-induced liver fibrosis model, subsequently, the levels of the PHD1, hypoxia-inducible factor-1α (HIF-1α), hypoxia-inducible factor-2α (HIF-2α), Keap1, and nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) were detected in liver tissues...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28538690/dysregulation-of-mirna-expression-in-cancer-associated-fibroblasts-cafs-and-its-consequences-on-the-tumor-microenvironment
#4
REVIEW
Maren Schoepp, Anda Jana Ströse, Jörg Haier
The tumor microenvironment, including cancer-associated fibroblasts (CAF), has developed as an important target for understanding tumor progression, clinical prognosis and treatment responses of cancer. Cancer cells appear to transform normal fibroblasts (NF) into CAFs involving direct cell-cell communication and epigenetic regulations. This review summarizes the current understanding on miR involvement in cancer cell-tumor environment/stroma communication, transformation of NFs into CAFs, their involved targets and signaling pathways in these interactions; and clinical relevance of CAF-related miR expression profiles...
May 24, 2017: Cancers
https://www.readbyqxmd.com/read/28536261/the-let-7-lin28-axis-regulates-activation-of-hepatic-stellate-cells-in-alcoholic-liver-injury
#5
Kelly McDaniel, Li Huang, Keisaku Sato, Nan Wu, Tami Annable, Tianhao Zhou, Sugeily Ramos-Lorenzo, Ying Wan, Qiaobing Huang, Heather Francis, Shannon Glaser, Hidekazu Tsukamoto, Gianfranco Alpini, Fanyin Meng
The let-7/lin28 axis is associated with the regulation of key cellular regulatory genes known as microRNAs (miRNAs) in different human disorders and cancer development. This study evaluated the role of the let-7/lin28 axis in regulating a mesenchymal phenotype of hepatic stellate cells in alcoholic liver injury. We identified that ethanol feeding significantly downregulated several members of the let-7 family in mouse liver, including let-7a and let-7b. Similarly, the treatment of human hepatic stellate cells (hHSCs) with lipopolysaccharide (LPS) and TGF-β significantly decreased the expressions of let-7a and let-7b...
May 23, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28534957/grape-seed-proanthocyanidin-inhibits-inflammatory-responses-in-hepatic-stellate-cells-by-modulating-the-mapk-akt-and-nf-%C3%AE%C2%BAb-signaling-pathways
#6
Jin-Woo Lee, Young Il Kim, Youngchul Kim, Minji Choi, Seoyeon Min, Yong Hoon Joo, Sung-Vin Yim, Namhyun Chung
In the present study, we aimed to investigate the molecular mechanisms and prophylactic effects of grape seed proanthocyanidin (GSP) on lipopolysaccharide (LPS)-stimulated human hepatic stellate cells (HSCs). Cell counting and MTT assays were used to assess cell viability in the absence or presence of GSP. Reverse transcription-quantitative PCR (RT-qPCR) was performed for several inflammation-related genes (NOD1, NOD2, TLR2, TLR4, IL-1 β, IL-6, IL-8, iNOS and COX-2). The expression of anti-inflammatory cell signaling molecules, including c-Jun N-terminal kinase (JNK), p38, extracellular signal regulated kinase (ERK), Akt, nuclear factor-κB (NF-κB), inhibitory-κBα (IκBα), iNOS and COX-2, was evaluated by western blot analysis...
May 19, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28531915/bone-marrow-stem-cells-anti-liver-fibrosis-potency-inhibition-of-hepatic-stellate-cells-activity-and-extracellular-matrix-deposition
#7
Ervina Julien Sitanggang, Radiana Dhewayani Antarianto, Sri Widia A Jusman, Jeanne Adiwinata Pawitan, Ahmad Aulia Jusuf
Transplantation of bone marrow derived stem cells (BMSCs) has been reported inhibits liver fibrosis. Several in vitro studies by co-culturing BMSCs and hepatic stellate cells (HSCs) indirectly or directly in 2D models showed inhibition of HSC as the key player in liver fibrosis. In this study, we investigated direct effect of BMSCs on HSCs by co-culturing BMSCs and HSCs in 3D model as it represents the liver microenvironment with intricate cell-cell and cell-matrix interactions. Primary isolated rat HSCs and BMSCs were directly co-cultured at 1:1 ratio with hanging drop method...
May 30, 2017: International Journal of Stem Cells
https://www.readbyqxmd.com/read/28527913/von-willebrand-factor-deficiency-reduces-liver-fibrosis-in-mice
#8
Nikita Joshi, Anna K Kopec, Jessica L Ray, Holly Cline-Fedewa, Dafna J Groeneveld, Ton Lisman, James P Luyendyk
Liver diseases are associated with complex changes in the hemostatic system and elevated levels of the platelet-adhesive protein Von Willebrand factor (VWF) are reported in patients with acute and chronic liver damage. Although elevated levels of VWF are associated with fibrosis in the general population, the role of VWF in acute and chronic liver injury has not been examined in depth in experimental settings. We tested the hypothesis that VWF deficiency inhibits experimental liver injury and fibrosis. Wild-type (WT) and VWF-deficient mice were challenged with carbon tetrachloride (CCl4) and the impact of VWF deficiency on acute liver injury and chronic liver fibrosis was determined...
May 17, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28526827/activated-hepatic-stellate-cells-secrete-periostin-to-induce-stem-cell-like-phenotype-of-residual-hepatocellular-carcinoma-cells-after-heat-treatment
#9
Rui Zhang, Rong-Rong Yao, Jing-Huan Li, Gang Dong, Min Ma, Qiong-Dan Zheng, Dong-Mei Gao, Jie-Feng Cui, Zheng-Gang Ren, Rong-Xin Chen
Some evidences show that residual tumor after thermal ablation will progress rapidly. However, its mechanisms remain unclear. Here, we assessed whether activated HSCs could regulate stem cell-like property of residual tumor after incomplete thermal ablation to promote tumor progression. Human HCC cell lines were exposed to sublethal heat treatment to simulate the peripheral zone of thermal ablation. After residual HCC cells were cultured with conditional medium (CM) from activated HSCs, parameters of the stem cell-like phenotypes were analyzed...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28525892/rasal1-is-a-potent-regulator-of-hepatic-stellate-cell-activity-and-liver-fibrosis
#10
Akemi Takata, Motoyuki Otsuka, Takahiro Kishikawa, Mari Yamagami, Rei Ishibashi, Kazuma Sekiba, Tatsunori Suzuki, Motoko Ohno, Yui Yamashita, Takaya Abe, Ryota Masuzaki, Tsuneo Ikenoue, Kazuhiko Koike
Liver fibrosis, leading to cirrhosis and liver failure, can occur after chronic liver injury. The transition of hepatic stellate cells (HSCs) from quiescent cells into proliferative and fibrogenic cells is a central event in liver fibrosis. Here, we show that RAS protein activator like-1 (RASAL1), a RAS-GTPase-activating protein, which switches off RAS activity, is significantly decreased during HSC activation, and that HSC activation can be antagonized by forced expression of the RASAL1 protein. We demonstrate that RASAL1 suppresses HSC proliferation by regulating the Ras-MAPK pathway, and that RASAL1 suppresses HSC fibrogenic activity by regulating the PKA-LKB1-AMPK-SRF pathway by interacting with angiotensin II receptor, type 1...
May 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28520165/targeting-ccl4-induced-liver-fibrosis-by-rna-interference-mediated-inhibition-of-cyclin-e1-in-mice
#11
Jörg-Martin Bangen, Linda Hammerich, Roland Sonntag, Maike Baues, Ute Haas, Daniela Lambertz, Thomas Longerich, Twan Lammers, Frank Tacke, Christian Trautwein, Christian Liedtke
Initiation and progression of liver fibrosis requires proliferation and activation of resting hepatic stellate cells (HSC). Cyclin E1 (CcnE1) is the regulatory subunit of the Cyclin-dependent Kinase 2 (Cdk2) and controls cell cycle re-entry. We have recently shown that genetic inactivation of CcnE1 prevents activation, proliferation and survival of HSC and protects from liver fibrogenesis. The aim of the present study was to translate these findings into pre-clinical applications using an RNAi-based approach...
May 18, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28518142/mir-130a-3p-attenuates-activation-and-induces-apoptosis-of-hepatic-stellate-cells-in-nonalcoholic-fibrosing-steatohepatitis-by-directly-targeting-tgfbr1-and-tgfbr2
#12
Yang Wang, Jinghua Du, Xuemin Niu, Na Fu, Rongqi Wang, Yuguo Zhang, Suxian Zhao, Dianxing Sun, Yuemin Nan
Nonalcoholic fibrosing steatohepatitis is a uniform process that occurs throughout nonalcoholic fatty liver disease (NAFLD). MicroRNAs (miRNAs) have been shown to be involved in the biological processes, but the role and molecular mechanism of miRNAs in NAFLD are not entirely clear. In this study, we observed a significant reduction in the expression of miR-130a-3p in livers of a mouse model with fibrosis induced by a methionine-choline-deficient diet, of NAFLD patients, and in activated hepatic stellate cells (HSCs)...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28508586/role-and-regulation-of-autophagy-and-apoptosis-by-nitric-oxide-in-hepatic-stellate-cells-during-acute-liver-failure
#13
Li Jin, Heng Gao, JiuPing Wang, ShuJuan Yang, Jing Wang, JingFeng Liu, Yuan Yang, TaoTao Yan, Tianyan Chen, Yingren Zhao, Yingli He
BACKGROUND & AIMS: We previously found that hepatic stellate cell (HSC) activation induced by autophagy maintains the liver architecture to prevent collapse during acute liver failure (ALF). Nitric oxide (NO) has shown to induce HSC apoptosis. Whether and how NO is involved in ALF and autophagy remains unclear. METHODS: ALF patients were recruited to investigate the correlation between plasma NO levels and clinical features. Liver tissues were collected from chronic hepatitis patients by biopsy and from ALF patients who had undergone liver transplantation...
May 15, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28506744/hepatic-stellate-cells-as-key-target-in-liver-fibrosis
#14
Takaaki Higashi, Scott L Friedman, Yujin Hoshida
Progressive liver fibrosis, induced by chronic viral and metabolic disorders, leads to more than one million deaths annually via development of cirrhosis, although no antifibrotic therapy has been approved to date. Transdifferentiation (or "activation") of hepatic stellate cells is the major cellular source of matrix protein-secreting myofibroblasts, the major driver of liver fibrogenesis. Paracrine signals from injured epithelial cells, fibrotic tissue microenvironment, immune and systemic metabolic dysregulation, enteric dysbiosis, and hepatitis viral products can directly or indirectly induce stellate cell activation...
May 12, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28506098/long-term-influence-of-sialoadenectomy-on-the-liver-of-male-albino-rat
#15
Abeer A Mahmoud, Ebtehal Z Hassan, Eman M Askar
Epidermal growth factor is an endocrine product of the submandibular gland; the liver is an important target of its action and is affected by sialoadenectomy. Thirty rats were used in this study and divided into group I (sham-operated animals), group II (sialoadenectomy after 4 weeks), and group III (sialoadenectomy after 10 weeks). Liver samples were processed for light and electron microscope examination. Sialoadenectomy induced mild-to-moderate liver damage which persists up to 10 weeks after the operation...
May 16, 2017: Ultrastructural Pathology
https://www.readbyqxmd.com/read/28504959/casticin-attenuates-liver-fibrosis-and-hepatic-stellate-cell-activation-by-blocking-tgf-%C3%AE-smad-signaling-pathway
#16
Ling Zhou, Xiaoying Dong, Linlin Wang, Lanlan Shan, Ting Li, Wanfu Xu, Yan Ding, Mingqiang Lai, Xiaojun Lin, Meng Dai, Xiaochun Bai, Chunhong Jia, Hang Zheng
Although many advances have been made in understanding the pathogenesis of liver fibrosis, few options are available for treatment. Casticin, one of the major flavonoids in Fructus Viticis extracts, has shown hepatoprotective potential, but its effects on liver fibrosis are not clear. In this study, we investigated the antifibrotic activity of casticin and its underlying mechanism in vivo and in vitro. Male mice were injected intraperitoneally with carbon tetrachloride (CCl4) or underwent bile duct ligation (BDL) to induce liver fibrosis, followed by treatment with casticin or vehicle...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28504685/spleen-derived-lipocalin-2-in-the-portal-vein-regulates-kupffer-cells-activation-and-attenuates-the-development-of-liver-fibrosis-in-mice
#17
Tomonori Aoyama, Kyoko Kuwahara-Arai, Akira Uchiyama, Kazuyoshi Kon, Hironao Okubo, Shunhei Yamashina, Kenichi Ikejima, Shigehiro Kokubu, Akihisa Miyazaki, Sumio Watanabe
The liver has an immune tolerance against gut-derived products from the portal vein (PV). A disruption of the gut-liver axis leads to liver injury and fibrosis. The spleen is connected to the PV and regulates immune functions. However, possible splenic effects on liver fibrosis development are unclear. Lipocalin-2 (Lcn2) is an antimicrobial protein that regulates macrophage activation. To clarify the role of the spleen in liver fibrosis development, we induced liver fibrosis in mice after splenectomy, and investigated liver fibrosis development...
May 15, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28502477/knockdown-of-hepatic-gonadotropin-releasing-hormone-by-vivo-morpholino-decreases-liver-fibrosis-in-multidrug-resistance-gene-2-knockout-mice-by-down-regulation-of-mir-200b
#18
Konstantina Kyritsi, Fanyin Meng, Tianhao Zhou, Nan Wu, Julie Venter, Heather Francis, Lindsey Kennedy, Paolo Onori, Antonio Franchitto, Francesca Bernuzzi, Pietro Invernizzi, Kelly McDaniel, Romina Mancinelli, Domenico Alvaro, Eugenio Gaudio, Gianfranco Alpini, Shannon Glaser
Hepatic fibrosis occurs during the progression of primary sclerosing cholangitis (PSC) and is characterized by accumulation of extracellular matrix proteins. Proliferating cholangiocytes and activated hepatic stellate cells (HSCs) participate in the promotion of liver fibrosis during cholestasis. Gonadotropin-releasing hormone (GnRH) is a trophic peptide hormone synthesized by hypothalamic neurons and the biliary epithelium and exerts its biological effects on cholangiocytes by interaction with the receptor subtype (GnRHR1) expressed by cholangiocytes and HSCs...
May 11, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28501125/direct-orthotopic-implantation-of-hepatic-organoids
#19
Vivian X Zhou, Macarena Lolas, Tammy T Chang
BACKGROUND: Liver organoids show potential for development as a tissue replacement therapy for patients with end-stage liver disease, but efficient methods for introducing organoids into host livers have not been established. In this study, we aimed to develop a surgical technique to implant hepatic organoids into the liver and assess their engraftment. METHODS: Donor hepatocytes were isolated from ROSA26 C57BL/6 mice, so that engrafted cells, when implanted into wild-type mice, could be easily identified by X-gal staining...
May 1, 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28498509/molecular-interplays-in-hepatic-stellate-cells-apoptosis-senescence-and-phenotype-reversion-as-cellular-connections-that-modulates-liver-fibrosis
#20
REVIEW
Silva B O, Ramos L F, Moraes K C M
Liver fibrosis is a pathophysiological process correlated with intense repair and cicatrization mechanisms in injured liver, and over the past few years, the characterization of the fine-tuning of molecular interconnections that support the development of liver fibrosis has been investigated. In this cellular process, the hepatic stellate cells (HSCs) support the organ fibrogenesis. The HSCs are found in two distinct morpho-physiological states: quiescent and activated. In normal liver, most HSCs are found in quiescent state, presenting a considerable amount of lipid droplets in the cytoplasm, while in injured liver the activated phenotype of HSCs is a myofibroblast,that secretes extracellular matrix elements and contributes to the establishment of the fibrotic process...
May 12, 2017: Cell Biology International
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