Article
Pharmacology & Pharmacy
Rubii Kondo, Akari Deguchi, Naoki Kawata, Yoshiaki Suzuki, Hisao Yamamura
Summary: This study investigates the role of TREK1 channels in hepatic stellate cells (HSCs) and their impact on membrane potential, calcium concentration, extracellular matrix production, and cell proliferation. The findings suggest that TREK1 channels play a crucial role in the molecular mechanism underlying hepatic fibrosis and may serve as a potential therapeutic target.
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2022)
Article
Cell Biology
Hwansu Kang, Eunhui Seo, Yoon Sin Oh, Hee-Sook Jun
Summary: Inflammation contributes to liver disease, and inflammasome activation plays a major role in amplifying liver inflammation. This study investigated the involvement of transforming growth factor-beta (TGF-beta) in inflammasome-mediated fibrosis in hepatic stellate cells. The results showed that TGF-beta increased the activation of NLRP3 inflammasome signaling and the expression of p-Smad2/3-NOX4, leading to increased ROS content and NLRP3 inflammasome activation. NEK7 and active caspase-1 expression were also elevated in TGF-beta-induced cells. Furthermore, TGF-beta secretion levels were significantly increased, and IL-1 beta receptor antagonist treatment inhibited its production. These findings suggest that TGF-beta may act as a danger signal to activate the NLRP3 inflammasome in an autocrine manner, and targeting the NLRP3 inflammasome could be a promising approach for treating TGF-beta-induced liver fibrosis.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2022)
Article
Cell Biology
Kiara Gaeberlein, Sarah K. Schroeder, Indrajit Nanda, Claus Steinlein, Thomas Haaf, Eva M. Buhl, Patrick Sauvant, Vincent Sapin, Armand Abergel, Ralf Weiskirchen
Summary: The rat hepatic stellate cell line PAV-1, established two decades ago, is a cellular model for studying hepatic retinoic acid metabolism. Despite being able to store retinyl esters and synthesize retinoic acid, this cell line has been overlooked. Genetically characterized established cell lines, like PAV-1, are valuable for biomedical research as working with in vivo models becomes more complicated.
Article
Cell Biology
Sarah K. Schroeder, Herdit M. Schueler, Kamilla Petersen, Cinzia Tesauro, Birgitta R. Knudsen, Finn S. Pedersen, Frederike Krus, Eva M. Buhl, Elke Roeb, Martin Roderfeld, Radovan Borojevic, Jamie L. Almeida, Ralf Weiskirchen
Summary: The GRX cell line, established from livers of mice infected with Schistosoma mansoni, displays a myofibroblast phenotype and can acquire a fat-storing lipocyte phenotype. Genetic characterization revealed chromosomal aberrations and the presence of viral particles belonging to the Retroviridae family. The cell line lacks S. mansoni-specific glycostructures. These findings are important for cell authentication and to avoid misinterpretation of experimental results.
Article
Cell Biology
Indrajit Nanda, Claus Steinlein, Thomas Haaf, Eva M. Buhl, Domink G. Grimm, Scott L. Friedman, Steffen K. Meurer, Sarah K. Schroeder, Ralf Weiskirchen
Summary: Immortalized hepatic stellate cells (HSCs) are valuable tools for liver biology research, but their use has some drawbacks, such as genetic drift and cell misidentification. This study characterizes the genetic features of the rat HSC line HSC-T6 and proposes cell line authentication.
Article
Cell Biology
Indrajit Nanda, Sarah K. Schroeder, Claus Steinlein, Thomas Haaf, Eva M. Buhl, Domink G. Grimm, Ralf Weiskirchen
Summary: Hepatic stellate cells (HSCs) are liver-specific mesenchymal cells that play a key role in maintaining the liver sinusoid microenvironment. Cultured HSCs are valuable tools for studying liver diseases, but their isolation requires special equipment and trained personnel. To overcome these limitations, immortalized HSC lines, such as CFSC, have been established.
Article
Biochemistry & Molecular Biology
Jack P. Carson, Mark W. Robinson, Grant A. Ramm, Geoffrey N. Gobert
Summary: This study identified the significantly deregulated genes and signaling pathways in LX-2 cells following TGF-beta 1 treatment. Some highly deregulated genes with no currently characterized role in HSC activation were discovered, potentially representing novel mediators of fibrotic responses in HSCs or the liver macroenvironment. This research may aid in identifying new markers of liver fibrosis and provide insights into prospective genes or pathways for potential future targeting in the amelioration of fibrotic liver disease.
MOLECULAR BIOLOGY REPORTS
(2021)
Article
Pharmacology & Pharmacy
Rubii Kondo, Naoki Kawata, Yoshiaki Suzuki, Hisao Yamamura
Summary: This study reveals the functional expression of Ca2+-sensing receptors (CaSRs) in activated hepatic stellate cells (HSCs) and demonstrates their role in regulating Ca2+ signaling and cell proliferation. These findings are important for understanding the molecular mechanisms underlying hepatic fibrosis and developing potential therapeutic targets.
BIOLOGICAL & PHARMACEUTICAL BULLETIN
(2022)
Article
Cell Biology
Wei Wang, Fangfang Li, Xiaoyang Lai, Han Liu, Shuting Wu, Yunqin Han, Yunfeng Shen
Summary: The study revealed that exosomes derived from palmitic acid-treated hepatocytes enriched in miR-107 played a dual role in regulating LX-2 cell activation, both by activating Wnt signaling in LX-2 cells and promoting activation through Raf/MEK/ERK signaling pathway by targeting Foxp1 in CD4+T lymphocytes.
CELL DEATH DISCOVERY
(2021)
Article
Biotechnology & Applied Microbiology
Ho-Joon Lee, Seon Ju Mun, Cho-Rok Jung, Hyun-Mi Kang, Jae-Eun Kwon, Jae-Sung Ryu, Hyo-Suk Ahn, Ok-Seon Kwon, Jiwon Ahn, Kyung-Sik Moon, Myung Jin Son, Kyung-Sook Chung
Summary: This study established and characterized a novel human hepatic stellate cell line (LSC-1) and used it in various three-dimensional co-culture systems with differentiated HepaRG cells. Comparisons with a commercially available HSC line on monolayer culture showed that LSC-1 exhibited upregulation of fibrogenic genes and increased levels of matrix and adhesion proteins. LSC-1 also had positive effects on co-cultured differentiated HepaRG and showed enhanced responsiveness to transforming growth factor beta 1 exposure in 3D spheroid culture.
BIOTECHNOLOGY AND BIOENGINEERING
(2023)
Article
Cell Biology
Brandon T. Wesley, Alexander D. B. Ross, Daniele Muraro, Zhichao Miao, Sarah Saxton, Rute A. Tomaz, Carola M. Morell, Katherine Ridley, Ekaterini D. Zacharis, Sandra Petrus-Reurer, Judith Kraiczy, Krishnaa T. Mahbubani, Stephanie Brown, Jose Garcia-Bernardo, Clara Alsinet, Daniel Gaffney, Dave Horsfall, Olivia C. Tysoe, Rachel A. Botting, Emily Stephenson, Dorin-Mirel Popescu, Sonya MacParland, Gary Bader, Ian D. McGilvray, Daniel Ortmann, Fotios Sampaziotis, Kourosh Saeb-Parsy, Muzlifah Haniffa, Kelly R. Stevens, Matthias Zilbauer, Sarah A. Teichmann, Ludovic Vallier
Summary: In this study, the developmental trajectories of human fetal liver cell types were described at single-cell resolution, and bipotential hepatoblast organoids were generated. This provides a platform for investigating human liver development and producing cell types for clinical applications.
NATURE CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Koichi Fujisawa, Yuto Nishimura, Akino Sakuragi, Jolien Duponselle, Toshihiko Matsumoto, Naoki Yamamoto, Tomoaki Murata, Isao Sakaida, Taro Takami
Summary: Research has been conducted to develop new medical treatments by simulating environments existing in space, such as zero-gravity. In this study, cell proliferation and gene expression of activated primary human hepatic stellate cells (HHSteCs) under simulated microgravity (SMG) were evaluated. The findings showed slower cell proliferation under SMG conditions, as well as changes in gene expression and oxidative stress. Upstream regulators were activated and cell-permeable inhibitors were inhibited, and cytoskeletal changes were observed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Endocrinology & Metabolism
James K. Carter, Scott L. Friedman
Summary: Nonalcoholic fatty liver disease (NAFLD) is the main cause of liver disease worldwide, and nonalcoholic steatohepatitis (NASH) is a more severe form characterized by significant hepatocellular injury, inflammation, and fibrosis. Recent research has shown that heightened immune cell activity and chronic inflammation play crucial roles in the development of NASH, with hepatic stellate cells (HSCs) being the key drivers of fibrosis.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Cell Biology
Haiying Liu, Linyu Dai, Ming Wang, Fumin Feng, Yonghong Xiao
Summary: This study demonstrated that tunicamycin can induce the apoptosis of HSCs by increasing intracellular Ca2+ concentration and enhancing the expression of ERS proteins, while decreasing the expression of antiapoptotic proteins. The findings suggest that tunicamycin induces HSC apoptosis through the calpain-2/Ca2+-dependent ERS pathway.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Food Science & Technology
Changting Wang, Zhiming Su, Jian-Hua Xu, Chih-Yuan Ko
Summary: Liver fibrosis and cirrhosis are primarily caused by the activation of hepatic stellate cells (HSCs), and Danshensu (Dan) can attenuate HSCs activation by regulating ferroptosis, thereby reducing liver fibrosis. These findings are important for understanding the mechanism of liver fibrosis and exploring potential therapeutic strategies.
FOOD SCIENCE & NUTRITION
(2023)
Letter
Gastroenterology & Hepatology
Ralf Weiskirchen
Article
Cell Biology
Joerg Weimer, Martje Huettmann, Asiyan Nusilati, Svenja Andreas, Jona Roeseler, Nils Tribian, Christoph Rogmans, Matthias Bernhard Stope, Edgar Dahl, Alexander Mustea, Elmar Stickeler, Nina Hedemann, Inken Floerkemeier, Katharina Tiemann, Svetlana Magadeeva, Astrid Dempfle, Norbert Arnold, Nicolai Maass, Dirk Bauerschlag
Summary: Endometrial cancer (EC) is a common gynaecological malignancy with increasing incidence. Hysteroscopy confirms only 30% of suspected ECs, but a non-invasive EC-FISH Test using smear test samples shows promise in reducing invasive procedures. By using aCGH, most frequently imbalanced genomic regions were identified in endometrial carcinomas, and FISH probes were generated to detect EC cells in vaginal swabs. The EC-FISH Test distinguishes patients with and without EC with a sensitivity of 91% and a specificity of 83% in a validation cohort.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2023)
Article
Chemistry, Multidisciplinary
Okan Tezcan, Asmaa Said Elshafei, Karina Benderski, Elena Rama, Maike Wagner, Diana Moeckel, Robert Pola, Michal Pechar, Tomas Etrych, Saskia von Stillfried, Fabian Kiessling, Ralf Weiskirchen, Steffen Meurer, Twan Lammers
Summary: Multidrug resistance (MDR) reduces the efficacy of chemotherapy by inducing drug efflux pumps and altering the tumor microenvironment (TME) composition, limiting drug delivery. Multidrug-resistant tumors displayed a more mesenchymal phenotype, increased collagen production, enriched TME, and enhanced vascular perfusion. Drug carriers accumulated more efficiently in resistant tumors but had a limited ability to penetrate the interstitium. Microenvironmental drug resistance affected liposomal doxorubicin performance more than free doxorubicin.
JOURNAL OF CONTROLLED RELEASE
(2023)
Review
Nutrition & Dietetics
Bodo C. C. Melnik, Swen Malte John, Pedro Carrera-Bastos, Loren Cordain, Claus Leitzmann, Ralf Weiskirchen, Gerd Schmitz
Summary: This review evaluates the impact of cow milk on breast carcinogenesis by linking recent epidemiological evidence and new insights into the molecular signaling of milk and its constituents in breast cancer pathogenesis. Recent prospective cohort studies support the association between cow's milk consumption and the risk of estrogen receptor-alpha-positive breast cancer. Milk contains various components that can increase systemic insulin-like growth factor 1, insulin, and estrogen signaling, promoting breast cancer. Potential oncogenic components of commercial milk include exosomal microRNAs, bovine meat and milk factors, aflatoxin M1, bisphenol A, pesticides, and micro- and nanoplastics. Individuals with certain gene mutations and genetic polymorphisms may be at increased risk for milk-induced breast cancer.
CURRENT NUTRITION REPORTS
(2023)
Review
Pharmacology & Pharmacy
Guoxun Chen, Sabine Weiskirchen, Ralf Weiskirchen
Summary: Vitamin A is a micronutrient that plays crucial roles in vision, cell growth, reproduction, and immunity. Deficiency and excess consumption of vitamin A both have severe health consequences. Despite being the first lipophilic vitamin discovered over a century ago and the definition of its biological roles, there are still unresolved issues related to vitamin A.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Immunology
Sandro Capellmann, Roland Sonntag, Herdit Schueler, Steffen K. Meurer, Lin Gan, Marlies Kauffmann, Katharina Horn, Hiltrud Koenigs-Werner, Ralf Weiskirchen, Christian Liedtke, Michael Huber
Summary: Mast cells (MCs) are heterogeneous immune cells with different protease repertoires and receptor expressions. A new cell line, PMC-306, derived from primary peritoneal MCs, can be used to study PMC function and tumorigenic processes associated with MC leukemia.
FRONTIERS IN IMMUNOLOGY
(2023)
Editorial Material
Cell Biology
Ralf Weiskirchen
JOURNAL OF CELL COMMUNICATION AND SIGNALING
(2023)
Article
Cell Biology
Erawan Borkham-Kamphorst, Steffen K. Meurer, Ralf Weiskirchen
Summary: The CCN protein family plays important biological functions in cell adhesion, migration, cell cycle progression, and control of extracellular matrix production and degradation. In the liver, CCN proteins are particularly involved in hepatic injury, disease, and remodeling. This study focused on CCN5/WISP2 and found that it is highly expressed in hepatic stellate cells, myofibroblasts, and portal myofibroblasts, while it is absent in hepatocytes. CCN5 upregulation during hepatic fibrosis induces endoplasmic reticulum stress, unfolded protein response, and apoptosis in portal myofibroblasts, potentially acting as a control mechanism against excessive fibrotic responses.
JOURNAL OF CELL COMMUNICATION AND SIGNALING
(2023)
Article
Cell Biology
Kiara Gaeberlein, Sarah K. Schroeder, Indrajit Nanda, Claus Steinlein, Thomas Haaf, Eva M. Buhl, Patrick Sauvant, Vincent Sapin, Armand Abergel, Ralf Weiskirchen
Summary: The rat hepatic stellate cell line PAV-1, established two decades ago, is a cellular model for studying hepatic retinoic acid metabolism. Despite being able to store retinyl esters and synthesize retinoic acid, this cell line has been overlooked. Genetically characterized established cell lines, like PAV-1, are valuable for biomedical research as working with in vivo models becomes more complicated.
Review
Cell Biology
Sabine Weiskirchen, Sarah K. K. Schroeder, Eva Miriam Buhl, Ralf Weiskirchen
Summary: The cultivation of cells in a favorable artificial environment has become an essential tool in cellular and molecular biology research. However, cell lines are often affected by misidentification, contamination, and specific biological and chemical hazards. This review offers an introduction to common problems encountered in cell culture laboratories and provides guidelines for preventing and addressing these issues.
Review
Biochemistry & Molecular Biology
Isabella Lurje, Nadine T. Gaisa, Ralf Weiskirchen, Frank Tacke
Summary: Fibrosis, a pathological scar tissue formation, can occur in various organs due to different etiologies and contributes to global morbidity and mortality. Common mechanisms involve sustained injury to parenchymal cells triggering a deregulated wound healing response. The transformation of fibroblasts into myofibroblasts with excessive extracellular matrix production is a hallmark of the disease, along with complex cellular interactions involving immune cells, endothelial cells, and parenchymal cells. Mediators such as growth factors, cytokines, and danger-associated molecular patterns play important roles in fibrosis across organs.
MOLECULAR ASPECTS OF MEDICINE
(2023)
Article
Cell Biology
Julia Otto, Anna Verwaayen, Christian Penners, Jana Hundertmark, Cheng Lin, Carina Kallen, Daniela Paffen, Tobias Otto, Hilmar Berger, Frank Tacke, Ralf Weiskirchen, Yulia A. Nevzorova, Matthias Bartneck, Christian Trautwein, Roland Sonntag, Christian Liedtke
Summary: Hepatocellular carcinoma (HCC) is a severe malignancy with limited treatment options. The development of HCC involves chronic liver inflammation and liver fibrosis. This study reveals the role of Cyclin E1 (CCNE1) and Cdk2 genes in Hepatic Stellate Cells (HSCs) in liver fibrogenesis and hepatocarcinogenesis.
CELL DEATH & DISEASE
(2023)
Review
Immunology
Sarah K. Schroeder, Natalie Gasterich, Sabine Weiskirchen, Ralf Weiskirchen
Summary: Human 25-kDa Lipocalin 2 (LCN2) was initially thought to be a circulating protein that transports small lipophilic molecules. However, further studies have shown its bacteriostatic properties, involvement in innate immunity, and regulation of various biological processes. The understanding of LCN2 receptors and their mechanisms is still lacking.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Marinela Krizanac, Paola Berenice Mass Sanchez, Sarah K. Schroeder, Ralf Weiskirchen, Anastasia Asimakopoulos
Summary: Perilipin 5 (PLIN5) is a lipid droplet coat protein highly expressed in oxidative tissues. It is regulated by peroxisome proliferator-activated receptors (PPARs) and cellular lipid status. Previous research focused on its role in non-alcoholic fatty liver disease (NAFLD) and lipid metabolism regulation. Limited studies connected PLIN5 to hepatocellular carcinoma (HCC), where its expression is upregulated. This study explores the regulation of PLIN5 by cytokines involved in HCC and NAFLD progression, revealing IL-6-induced upregulation mediated by the JAK/STAT3 signaling pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Letter
Gastroenterology & Hepatology
Ralf Weiskirchen
