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liver progenitor cell

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https://www.readbyqxmd.com/read/28073888/selective-targeting-of-lysyl-oxidase-like-2-loxl2-suppresses-hepatic-fibrosis-progression-and-accelerates-its-reversal
#1
Naoki Ikenaga, Zhen-Wei Peng, Kahini A Vaid, Susan B Liu, Shuhei Yoshida, Deanna Y Sverdlov, Amanda Mikels-Vigdal, Victoria Smith, Detlef Schuppan, Yury V Popov
BACKGROUND/AIMS: We studied the role of lysyl oxidase-like 2 (LOXL2) in collagen crosslinking and hepatic progenitor cell (HPC) differentiation, and the therapeutic efficacy of a LOXL2-blocking monoclonal antibody on liver fibrosis progression/reversal in mice. METHODS: Anti-LOXL2 antibody, control antilysyl oxidase antibody or placebo was administered during thioacetamide (TAA)-induced fibrosis progression or during recovery. Therapeutic efficacy in biliary fibrosis was tested in BALB/c...
January 10, 2017: Gut
https://www.readbyqxmd.com/read/28067405/lkb1-regulation-of-skeletal-muscle-development-metabolism-and-muscle-progenitor-cell-homeostasis
#2
REVIEW
Tizhong Shan, Ziye Xu, Jiaqi Liu, Weiche Wu, Yizhen Wang
Liver kinase B1 (Lkb1), also named as Serine/Threonine protein kinase 11 (STK11), is a serine/threonine kinase that plays crucial roles in various cellular processes including cell survival, cell division, cellular polarity, cell growth, cell differentiation, and cell metabolism. In metabolic tissues, Lkb1 regulates glucose homeostasis and energy metabolism through phosphorylating and activating the AMPK subfamily proteins. In skeletal muscle, Lkb1 affects muscle development and postnatal growth, lipid and fatty acid oxidation, glucose metabolism and insulin sensitivity...
January 9, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28056498/bone-marrow-stem-cell-therapy-partially-ameliorates-pathological-consequences-in-livers-of-mice-expressing-mutant-human-%C3%AE-1-antitrypsin
#3
Prakash Baligar, Veena Kochat, Shailendra K Arindkar, Zaffar Equbal, Snehashish Mukherjee, Swati Patel, Perumal Nagarajan, Sujata Mohanty, Jeffrey H Teckman, Asok Mukhopadhyay
: Alpha1-antitrypsin deficiency (AATD) is a genetic disease, caused by mutation of the AAT gene. Accumulation of mutated AAT protein aggregates in hepatocytes leads to endoplasmic reticulum (ER) stress resulting in impairment of liver functions and in some cases hepatocellular carcinoma, whereas decline of AAT levels in sera is responsible for pulmonary emphysema. In critical cases of liver ailments, the only option for treatment is liver transplantation, whereas AAT replacement therapy is followed in case of emphysema...
January 5, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28052241/modeling-dynamics-and-function-of-bone-marrow-cells-in-mouse-liver-regeneration
#4
Elisa Pedone, Vlad-Aris Olteanu, Lucia Marucci, Maria Isabel Muñoz-Martin, Sameh A Youssef, Alain de Bruin, Maria Pia Cosma
In rodents and humans, the liver can efficiently restore its mass after hepatectomy. This is largely attributed to the proliferation and cell cycle re-entry of hepatocytes. On the other hand, bone marrow cells (BMCs) migrate into the liver after resection. Here, we find that a block of BMC recruitment into the liver severely impairs its regeneration after the surgery. Mobilized hematopoietic stem and progenitor cells (HSPCs) in the resected liver can fuse with hepatocytes, and the hybrids proliferate earlier than the hepatocytes...
January 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28051157/progressive-induction-of-hepatocyte-progenitor-cells-in-chronically-injured-liver
#5
Naoki Tanimizu, Norihisa Ichinohe, Masahiro Yamamoto, Haruhiko Akiyama, Yuji Nishikawa, Toshihiro Mitaka
Differentiated epithelial cells show substantial lineage plasticity upon severe tissue injuries. In chronically injured mouse livers, part of hepatocytes become Sry-HMG box containing 9 (Sox9) (+) epithelial cell adhesion molecule (-) hepatocyte nuclear factor 4 α (+) biphenotypic hepatocytes. However, it is not clear whether all Sox9(+) hepatocytes uniformly possess cellular properties as hepatocyte progenitors. Here, we examined the microarray data comparing Sox9(+) hepatocytes with mature hepatocytes and identified CD24 as a novel marker for biphenotypic hepatocytes...
January 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28043904/liver-cancer-cell-of-origin-molecular-class-and-effects-on-patient-prognosis
#6
REVIEW
Daniela Sia, Augusto Villanueva, Scott L Friedman, Josep M Llovet
Primary liver cancer is the second leading cause of cancer-related death worldwide and therefore a major public health challenge. We review hypotheses of the cell of origin of liver tumorigenesis, and clarify the classes of liver cancer, based on molecular features and how these affect patient prognosis. Primary liver cancer comprises hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and other rare tumors, notably fibrolamellar carcinoma and hepatoblastoma. The molecular and clinical features of HCC vs iCCA are distinct, although they have overlapping risk factors and pathways of oncogenesis...
December 30, 2016: Gastroenterology
https://www.readbyqxmd.com/read/28034754/lxr-agonists-promote-the-proliferation-of-neural-progenitor-cells-through-mek-erk-pathway
#7
Jing-Zhong Wang, Yan Fang, Wei-Dong Ji, Hui Xu
The liver X receptors (LXRs) are transcriptional regulators of lipid homeostasis and may be critical for neurodegeneration and neurogenesis in vivo. However, it remains largely unknown about the role of LXRs and its agonists in the in vitro proliferation of neural progenitor cells (NPCs). Here we revealed for the first time that LXRs were markedly expressed in mouse NPCs and were critical for the in vitro proliferation. LXR agonists GW3965 and LXR623 promoted the proliferation of wildtype NPCs, but not NPCs from LXR double-knockout mice...
December 26, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28028143/abca1-apoe-hdl-pathway-mediates-gw3965-induced-neurorestoration-after-stroke
#8
Xu Cui, Michael Chopp, Zhenggang Zhang, Rongwen Li, Alex Zacharek, Julie Landschoot-Ward, Poornima Venkat, Jieli Chen
BACKGROUND AND PURPOSE: ATP-binding cassette transporter A1 (ABCA1) is a major reverse cholesterol transporter and plays critical role in the formation of brain high-density lipoprotein (HDL) cholesterol. Apolipoprotein E (ApoE) is the most abundant apolipoprotein and transports cholesterol into cells in brain. ABCA1 and ApoE are upregulated by liver-X receptors. Activation of liver-X receptors has neurorestorative benefit for stroke. The current study investigates whether ABCA1/ApoE/HDL pathway mediates GW3965, a synthetic dual liver-X receptor agonist, induced neurorestoration after stroke...
December 27, 2016: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28026812/-the-hepatic-differentiation-of-adult-and-fetal-liver-stromal-cells-in-vitro
#9
I V Kholodenko, R V Kholodenko, G V Manukyan, K N Yarygin
The liver has a marked capacity for regeneration. In most cases the liver regeneration is determined by hepatocytes. The regenerative capacity of hepatocytes is significantly reduced in acute or chronic damage. In particular, repair mechanisms are not activated in patients with alcoholic cirrhosis. Organ transplantation or advanced methods of regenerative medicine can help such patients. The promising results were obtained in clinical trials involving patients with various forms of liver disease who received transplantation of autologous bone marrow stem cells...
November 2016: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/28025230/mechanisms-for-hepatobiliary-toxicity-in-rats-treated-with-an-antagonist-of-melanin-concentrating-hormone-receptor-1-mchr1
#10
Monicah A Otieno, Vasanthi Bhaskaran, Evan Janovitz, Yimer Callejas, William B Foster, William Washburn, John R Megill, Lois Lehman-McKeeman, Brian Gemzik
The objective of this work was to investigate the mechanisms of hepatobiliary toxicity caused by thienopyrimidone MCHR1 antagonists using BMS-773174 as a tool molecule. Co-administration of the pan CYP inhibitor 1-aminobenzotriazole with BMS-773174 prevented hepatobiliary damage, and direct delivery of the diol metabolite BMS-769750 caused hepatobiliary toxicity, identifying the diol and possibly its downstream hydroxyacid (BMS-800754) metabolite as the toxic species. Rat liver gene expression revealed treatment-related changes in hepatic transporters and induction of oval cell-specific genes including deleted malignant tumor 1 (Dmbt1)...
October 20, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/27997988/hepatostat-liver-regeneration-and-normal-liver-tissue-maintenance
#11
George K Michalopoulos
In contrast to all other organs, liver to body weight ratio needs to be maintained always at 100% of what is required for body homeostasis. Adjustment of liver size to 100% of what is required for homeostasis has been called "hepatostat". Removal of a portion of any other organ is followed with local regeneration of a limited degree, but it never attempts to reach 100% of the original size. The complex mechanisms involved in this uniquely hepatic process encompass a variety of regenerative pathways that are specific to different types of injury...
December 20, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27991908/early-activated-hepatic-stellate-cell-derived-paracrine-molecules-modulate-acute-liver-injury-and-regeneration
#12
Wenju Chang, Lujun Song, Xiujuan Chang, Meiling Ji, Hongshan Wang, Xinyu Qin, Weixin Niu
The effects of paracrine action from early activated hepatic stellate cells (HSCs) on resident liver epithelium cells are not clear. Here, we investigated whether a systemic infusion of early activated HSC-derived paracrine factors (HSC-CM) would evoke an enhanced liver protective response in acetaminophen (APAP)-induced acute liver injury (ALI) in mice and explored the possible underlying mechanisms. The survival rate, liver injury, and liver regeneration were analyzed in mice with or without HSC-CM treatment in vivo...
December 19, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27990610/existence-of-cancer-stem-cells-in-hepatocellular-carcinoma-myth-or-reality
#13
Keigo Machida
The cancer stem cell (CSC) hypothesis has been disproved in many cancers. CSCs may exist in blood cancer, while many epithelial cancers may not have CSCs but tumor-initiating cells (TICs). Several independent studies have provided strong evidence for existence of CSCs in brain, skin, and colon cancers (Mani et al. in Cell 133:704-715, 2008, Joseph et al. in Cancer Cell 13:129-140, 2008, Reya et al. in Nature 414:105-111, 2001), while the CSC hypothesis remains controversial (Magee et al. in Cancer Cell 21:283-296, 2012)...
December 18, 2016: Hepatology International
https://www.readbyqxmd.com/read/27974222/usp10-is-an-essential-deubiquitinase-for-hematopoiesis-and-inhibits-apoptosis-of-long-term-hematopoietic-stem-cells
#14
Masaya Higuchi, Hiroki Kawamura, Hideaki Matsuki, Toshifumi Hara, Masahiko Takahashi, Suguru Saito, Kousuke Saito, Shuying Jiang, Makoto Naito, Hiroshi Kiyonari, Masahiro Fujii
Self-renewal, replication, and differentiation of hematopoietic stem cells (HSCs) are regulated by cytokines produced by niche cells in fetal liver and bone marrow. HSCs must overcome stresses induced by cytokine deprivation during normal development. In this study, we found that ubiquitin-specific peptidase 10 (USP10) is a crucial deubiquitinase for mouse hematopoiesis. All USP10 knockout (KO) mice died within 1 year because of bone marrow failure with pancytopenia. Bone marrow failure in these USP10-KO mice was associated with remarkable reductions of long-term HSCs (LT-HSCs) in bone marrow and fetal liver...
December 13, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27959618/mechanisms-of-organ-injury-and-repair-by-macrophages
#15
Kevin M Vannella, Thomas A Wynn
Macrophages regulate tissue regeneration following injury. They can worsen tissue injury by producing reactive oxygen species and other toxic mediators that disrupt cell metabolism, induce apoptosis, and exacerbate ischemic injury. However, they also produce a variety of growth factors, such as IGF-1, VEGF-α, TGF-β, and Wnt proteins that regulate epithelial and endothelial cell proliferation, myofibroblast activation, stem and tissue progenitor cell differentiation, and angiogenesis. Proresolving macrophages in turn restore tissue homeostasis by functioning as anti-inflammatory cells, and macrophage-derived matrix metalloproteinases regulate fibrin and collagen turnover...
December 7, 2016: Annual Review of Physiology
https://www.readbyqxmd.com/read/27956903/comprehensive-screening-of-cell-surface-markers-expressed-by-adult-derived-human-liver-stem-progenitor-cells-harvested-at-passage-5-potential-implications-for-engraftment
#16
Pierre-Edouard Dollet, Joachim Ravau, Floriane André, Mustapha Najimi, Etienne Sokal, Catherine Lombard
Mesenchymal stromal cells (MSCs) are known to have potential therapeutic benefits for a number of diseases. However, many studies report low engraftment levels, regardless of the target organ. One possible explanation could be that MSCs do not express the necessary receptors for engraftment. Indeed, MSCs appear to use a similar mechanism to leukocytes to engraft into injured organs, relying on various receptors for rolling, firm adhesion, and transmigration. In this study, we conducted an extensive surface molecule screening of adult-derived human liver stem/progenitor cells (ADHLSC) in an attempt to shed some light on this subject...
2016: Stem Cells International
https://www.readbyqxmd.com/read/27956228/genome-wide-crispr-screen-identifies-regulators-of-mapk-as-suppressors-of-liver-tumors-in-mice
#17
Chun-Qing Song, Yingxiang Li, Haiwei Mou, Jill Moore, Angela Park, Yotsawat Pomyen, Soren Hough, Zachary Kennedy, Andrew Fischer, Hao Yin, Daniel G Anderson, Darryl Conte, Lars Zender, Xin Wei Wang, Snorri Thorgeirsson, Zhiping Weng, Wen Xue
BACKGROUND & AIMS: It has been a challenge to identify liver tumor suppressors or oncogenes due to the genetic heterogeneity of these tumors. We performed a genome-wide screen to identify suppressors of liver tumor formation in mice, using CRISPR-mediated genome editing. METHODS: We performed a genome-wide CRISPR/Cas9-based knockout screen of P53-null mouse embryonic liver progenitor cells that overexpressed MYC. We infected p53(-/-);Myc;Cas9 hepatocytes with the mGeCKOa lentiviral library of 67,000 single-guide RNAs (sgRNAs), targeting 20,611 mouse genes, and transplanted the transduced cells subcutaneously into nude mice...
December 9, 2016: Gastroenterology
https://www.readbyqxmd.com/read/27938502/novel-advances-in-understanding-of-molecular-pathogenesis-of-hepatoblastoma-a-wnt-beta-catenin-perspective
#18
Danielle Bell, Sarangarajan Ranganathan, Junyan Tao, Satdarshan Monga
Hepatoblastoma is the most common pediatric liver malignancy, typically striking children within the first 3 years of their young lives. While advances in chemotherapy and newer surgical techniques have improved survival in patients with localized disease, unfortunately, for the 25% of patients with metastasis, the overall survival remains poor. These tumors, which are thought to arise from hepatic progenitors or hepatoblasts, hence the name hepatoblastoma, can be categorized by histological subtyping based on their level of cell differentiation...
2, 2016: Gene Expression
https://www.readbyqxmd.com/read/27927101/development-of-erythroid-progenitors-under-erythropoietin-stimulation-in-xenopus-laevis-larval-liver
#19
Takehito Okui, Sakiko Hosozawa, Satoka Kohama, Shingo Fujiyama, Shun Maekawa, Hiroshi Muto, Takashi Kato
Erythroid progenitors that respond to erythropoietin (Epo) are present in the liver of adult Xenopus laevis. However, cells responding to Epo in the larval liver and through the metamorphosis period under hepatic remodeling have not been characterized. In this study, tadpoles were staged using the tables of Nieuwkoop and Faber (NF). Liver cells from pre- (NF56) or post- (NF66) metamorphic stage were cultured in the presence of Epo. β2-globin mRNA expression peaked at day 7 after the start of culture. Larval β2-globin was highly expressed in NF56-derived cells, while adult β2-globinwas detected in those of NF66...
December 2016: Zoological Science
https://www.readbyqxmd.com/read/27925343/transplantation-of-thy1-cells-accelerates-liver-regeneration-by-enhancing-the-growth-of-small-hepatocyte-like-progenitor-cells-via-il17rb-signaling
#20
Norihisa Ichinohe, Masayuki Ishii, Naoki Tanimizu, Junko Kon, Yusuke Yoshioka, Takahiro Ochiya, Toru Mizuguchi, Koichi Hirata, Toshihiro Mitaka
Small hepatocyte-like progenitor cells (SHPCs) transiently form clusters in rat livers treated with retrorsine (Ret)/70% partial hepatectomy (PH). When Thy1(+) cells isolated from d-galactosamine-treated rat livers were transplanted into the livers of Ret/PH-treated rats, the mass of the recipient liver transiently increased during the first 30 days after transplantation, suggesting that liver regeneration was enhanced. Here we addressed how Thy1(+) cell transplantation stimulates liver regeneration. We found that the number and size of SHPC clusters increased in the liver at 14 days after transplantation...
December 7, 2016: Stem Cells
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