Genetic Characteristics of the Human Hepatic Stellate Cell Line LX-2

Weiskirchen, Ralf; Weimer, Jörg; Meurer, Steffen K.; Kron, Anja; Seipel, Barbara; Vater, Inga; Arnold, Norbert; Siebert, Reiner; Xu, Li; Friedman, Scott L.; Bergmann, Carsten

doi:10.1371/journal.pone.0075692

Cited by 59 publications

(58 citation statements)

References 32 publications

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“…LX-2 human stellate cell line has been shown to have all the key features of activated HSC and has been used in numerous studies in hepatic fibrogenesis1617, and it expresses NOX4 (Suppl. Fig.…”

Section: Resultsmentioning

confidence: 99%

NOX4 Regulates CCR2 and CCL2 mRNA Stability in Alcoholic Liver Disease

Sasaki

Dehnad

Fish

et al. 2017

Sci Rep

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Recruitment of inflammatory cells is a major feature of alcoholic liver injury however; the signals and cellular sources regulating this are not well defined. C-C chemokine receptor type 2 (CCR2) is expressed by active hepatic stellate cells (HSC) and is a key monocyte recruitment signal. Activated HSC are also important sources of hydrogen peroxide resulting from the activation of NADPH oxidase 4 (NOX4). As the role of this NOX in early alcoholic liver injury has not been addressed, we studied NOX4-mediated regulation of CCR2/CCL2 mRNA stability. NOX4 mRNA was significantly induced in patients with alcoholic liver injury, and was co-localized with αSMA-expressing activated HSC. We generated HSC-specific NOX4 KO mice and these were pair-fed on alcohol diet. Lipid peroxidation have not changed significantly however, the expression of CCR2, CCL2, Ly6C, TNFα, and IL-6 was significantly reduced in NOX4HSCKO compared to fl/fl mice. NOX4 promoter was induced in HSC by acetaldehyde treatment, and NOX4 has significantly increased mRNA half-life of CCR2 and CCL2 in conjunction with Ser221 phosphorylation and cytoplasmic shuttling of HuR. In conclusion, NOX4 is induced in early alcoholic liver injury and regulates CCR2/CCL2 mRNA stability thereby promoting recruitment of inflammatory cells and production of proinflammatory cytokines.

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Section: Resultsmentioning

confidence: 99%

NOX4 Regulates CCR2 and CCL2 mRNA Stability in Alcoholic Liver Disease

Sasaki

Dehnad

Fish

et al. 2017

Sci Rep

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“…LX2 cells were obtained from SL Friedman (Mount Sani Medical School) ( 43,44 ). LX2 cells are activated human hepatic stellate cells; they are maintained in DMEM with 5% FCS containing penicillin, streptomycin, and normocin.…”

Section: Lx2 Cellsmentioning

confidence: 99%

“…Herein, we determine whether DHA can act directly on stellate cells to regulate TGF ␤ 1 control of Col1A1. LX2 cells are a human activated stellate cell line ( 43,44 ). We fi rst determined if LX2 cells assimilate and metabolize exogenous fatty acids.…”

Section: Dha Attenuates Tgf ␤ Induction Of Col1a1 In Lx2 Cellsmentioning

confidence: 99%

Docosahexaenoic acid attenuates Western diet-induced hepatic fibrosis in Ldlr mice by targeting the TGFβ-Smad3 pathway

Lytle

Depner

Wong

et al. 2015

Journal of Lipid Research

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This article is available online at http://www.jlr.org mainly as neutral lipids consisting of triacylglycerols, cholesterol esters, and diacylglycerols. NAFLD ranges in severity from benign hepatosteatosis to nonalcoholic steatohepatitis (NASH) ( 1 ). NASH is defi ned as hepatosteatosis with infl ammation and hepatic injury ( 2 ). Although simple hepatosteatosis is considered clinically benign, NASH is the progressive form of the disease that can lead to significant changes in hepatic morphology (hepatocyte ballooning) and injury (cell death and fi brosis).The incidence of NAFLD has increased in parallel with the obesity epidemic in Western societies. In the general population, the prevalence of NAFLD is estimated to range from 6 to 33% ( 3 ), and ‫ف‬ 30-40% of individuals with hepatic steatosis progress to NASH ( 4 ). The prevalence of NASH ranges from 3 to 5% in the general population ( 3 ). NAFLD and NASH have high prevalence ( у 60%) in patients with type 2 diabetes ( 5 ). Additionally, NASH patients have higher mortality rates than NAFLD patients ( 6-8 ), and over a 10 year period, cirrhosis and liver-related death occurs in 20 and 12% of NASH patients, respectively ( 9 ). Because NASH can progress to cirrhosis, hepatocellular cancer, and liver failure ( 4,(10)(11)(12)(13)(14), it is the third most common cause for liver transplantation. NASH is projected to be the leading cause of liver transplantation in the United States by 2020 ( 15 ).Hepatic fi brosis involves the increased production of extracellular matrix (ECM) from activated hepatic stellate cells and myofi broblasts infi ltrating the liver. The liver has an underlayment of connective tissue composed of several Nonalcoholic fatty liver disease (NAFLD) is a signifi cant public health burden in Western societies. NAFLD is defi ned as excess accumulation of liver fat (hepatosteatosis),

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“…Monocyte-derived macrophages were used to mimic Kupffer cell function and the immortalized human stellate cell line LX-2 as primary stellate cell surrogate. Immortalized cell lines have the advantage of continuous growth, unlimited availability and their clonal origin usually guarantees a constant phenotype allowing reproducible experimentation [23,24]. During culture in the biochip HepaRG cells consistently differentiate into cells exhibiting a hepatocyte phenotype and into cells with biliary epithelial cell phenotype that self-organize into a hepatocyte layer with functional bile ducts between hepatocyte-like cells [25] essential for liver function [26].…”

Section: Introductionmentioning

confidence: 99%