المؤلفون: Soumyadeep Sarkar, Cailin Deiter, Jennifer E. Kyle, Michelle A. Guney, Dylan Sarbaugh, Ruichuan Yin, Xiangtang Li, Yi Cui, Mireia Ramos-Rodriguez, Carrie D. Nicora, Farooq Syed, Jonas Juan-Mateu, Charanya Muralidharan, Lorenzo Pasquali, Carmella Evans-Molina, Decio L. Eizirik, Bobbie-Jo M. Webb-Robertson, Kristin Burnum-Johnson, Galya Orr, Julia Laskin, Thomas O. Metz, Raghavendra G. Mirmira, Lori Sussel, Charles Ansong, Ernesto S. Nakayasu

المصدر: Cell Communication and Signaling, Vol 22, Iss 1, Pp 1-17 (2024)

مصطلحات موضوعية: Medicine, Cytology, QH573-671

الوصف: Abstract Background Lipids are regulators of insulitis and β-cell death in type 1 diabetes development, but the underlying mechanisms are poorly understood. Here, we investigated how the islet lipid composition and downstream signaling regulate β-cell death. Methods We performed lipidomics using three models of insulitis: human islets and EndoC-βH1 β cells treated with the pro-inflammatory cytokines interlukine-1β and interferon-γ, and islets from pre-diabetic non-obese mice. We also performed mass spectrometry and fluorescence imaging to determine the localization of lipids and enzyme in islets. RNAi, apoptotic assay, and qPCR were performed to determine the role of a specific factor in lipid-mediated cytokine signaling. Results Across all three models, lipidomic analyses showed a consistent increase of lysophosphatidylcholine species and phosphatidylcholines with polyunsaturated fatty acids and a reduction of triacylglycerol species. Imaging assays showed that phosphatidylcholines with polyunsaturated fatty acids and their hydrolyzing enzyme phospholipase PLA2G6 are enriched in islets. In downstream signaling, omega-3 fatty acids reduce cytokine-induced β-cell death by improving the expression of ADP-ribosylhydrolase ARH3. The mechanism involves omega-3 fatty acid-mediated reduction of the histone methylation polycomb complex PRC2 component Suz12, upregulating the expression of Arh3, which in turn decreases cell apoptosis. Conclusions Our data provide insights into the change of lipidomics landscape in β cells during insulitis and identify a protective mechanism by omega-3 fatty acids. Video Abstract

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1478-811XTest

الوصول الحر: https://doaj.org/article/6b57b4f4064a4390ae8f0840effa40acTest

المؤلفون: Soumyadeep Sarkar, Cailin Deiter, Jennifer E. Kyle, Michelle A. Guney, Dylan Sarbaugh, Ruichuan Yin, Xiangtang Li, Yi Cui, Mireia Ramos-Rodriguez, Carrie D. Nicora, Farooq Syed, Jonas Juan-Mateu, Charanya Muralidharan, Lorenzo Pasquali, Carmella Evans-Molina, Decio L. Eizirik, Bobbie-Jo M. Webb-Robertson, Kristin Burnum-Johnson, Galya Orr, Julia Laskin, Thomas O. Metz, Raghavendra G. Mirmira, Lori Sussel, Charles Ansong, Ernesto S. Nakayasu

مصطلحات موضوعية: Biophysics, Biochemistry, Cell Biology, Genetics, Molecular Biology, Physiology, Immunology, Developmental Biology, Cancer, Hematology, Chemical Sciences not elsewhere classified, polyunsaturated fatty acids, lipidomic analyses showed, inflammatory cytokines interlukine, data provide insights, 3 fatty acids, 3 fatty acid, imaging assays showed, mediated cytokine signaling, islet lipid composition, mechanism involves omega, protective mechanism, fluorescence imaging, downstream signaling, video abstract, underlying mechanisms, triacylglycerol species, three models, specific factor, results across

الوصف: Additional file 1: Figure S1. Abundance of selected proteins from proteomics analysis of 3 common models used for the study of β-cell stress in type 1 diabetes: A EndoC-βH1 cells exposed to IL-1β and INF-γ for 48 h (n = 3), B human islets exposed to same cytokines for 24 h (n = 10) and C islets from non-obese diabetic (NOD) mice in pre-diabetic stage (6 weeks of age) vs. age-matched NOR mice (n = 3). Abbreviations: GBP2: interferon-induced guanylate-binding protein 2, Stat1: signal transducer and activator of transcription 1, TAP1: antigen peptide transporter 1. Statistical test: ** p ≤ 0.01 and *** p ≤ 0.001 by t-test considering equal distribution and variance.

العلاقة: https://figshare.com/articles/journal_contribution/Additional_file_1_of_Regulation_of_-cell_death_by_ADP-ribosylhydrolase_ARH3_via_lipid_signaling_in_insulitis/25264208Test

الإتاحة: https://doi.org/10.6084/m9.figshare.25264208.v1Test
https://figshare.com/articles/journal_contribution/Additional_file_1_of_Regulation_of_-cell_death_by_ADP-ribosylhydrolase_ARH3_via_lipid_signaling_in_insulitis/25264208Test

المؤلفون: Marta Fontcuberta-PiSunyer, Ainhoa García-Alamán, Èlia Prades, Noèlia Téllez, Hugo Alves-Figueiredo, Mireia Ramos-Rodríguez, Carlos Enrich, Rebeca Fernandez-Ruiz, Sara Cervantes, Laura Clua, Javier Ramón-Azcón, Christophe Broca, Anne Wojtusciszyn, Nuria Montserrat, Lorenzo Pasquali, Anna Novials, Joan-Marc Servitja, Josep Vidal, Ramon Gomis, Rosa Gasa

المصدر: Communications Biology, Vol 6, Iss 1, Pp 1-15 (2023)

مصطلحات موضوعية: Biology (General), QH301-705.5

الوصف: Human foreskin fibroblasts are directly reprogrammed into insulin-producing cells using 5 pancreatic transcription factors, without pluripotency induction.

العلاقة: https://doi.org/10.1038/s42003-023-04627-2Test; https://doaj.org/toc/2399-3642Test; https://doaj.org/article/29d2817f5dfe44d989d5e0fd8d306fdaTest

الإتاحة: https://doi.org/10.1038/s42003-023-04627-2Test
https://doaj.org/article/29d2817f5dfe44d989d5e0fd8d306fdaTest

المؤلفون: Noelia Arroyo, Laura Villamayor, Irene Díaz, Rita Carmona, Mireia Ramos-Rodríguez, Ramón Muñoz-Chápuli, Lorenzo Pasquali, Miguel G. Toscano, Franz Martín, David A. Cano, Anabel Rojas

المصدر: JCI Insight, Vol 6, Iss 23 (2021)

مصطلحات موضوعية: Cell biology, Gastroenterology, Medicine

الوصف: In response to liver injury, hepatic stellate cells activate and acquire proliferative and contractile features. The regression of liver fibrosis appears to involve the clearance of activated hepatic stellate cells, either by apoptosis or by reversion toward a quiescent-like state, a process called deactivation. Thus, deactivation of active hepatic stellate cells has emerged as a novel and promising therapeutic approach for liver fibrosis. However, our knowledge of the master regulators involved in the deactivation and/or activation of fibrotic hepatic stellate cells is still limited. The transcription factor GATA4 has been previously shown to play an important role in embryonic hepatic stellate cell quiescence. In this work, we show that lack of GATA4 in adult mice caused hepatic stellate cell activation and, consequently, liver fibrosis. During regression of liver fibrosis, Gata4 was reexpressed in deactivated hepatic stellate cells. Overexpression of Gata4 in hepatic stellate cells promoted liver fibrosis regression in CCl4-treated mice. GATA4 induced changes in the expression of fibrogenic and antifibrogenic genes, promoting hepatic stellate cell deactivation. Finally, we show that GATA4 directly repressed EPAS1 transcription in hepatic stellate cells and that stabilization of the HIF2α protein in hepatic stellate cells leads to liver fibrosis.

العلاقة: https://doi.org/10.1172/jci.insight.150059Test; https://doaj.org/toc/2379-3708Test; https://doaj.org/article/3d39efa050a44c909abdd4aba2f00be4Test

الإتاحة: https://doi.org/10.1172/jci.insight.150059Test
https://doaj.org/article/3d39efa050a44c909abdd4aba2f00be4Test

المؤلفون: Maikel L. Colli, Mireia Ramos-Rodríguez, Ernesto S. Nakayasu, Maria I. Alvelos, Miguel Lopes, Jessica L. E. Hill, Jean-Valery Turatsinze, Alexandra Coomans de Brachène, Mark A. Russell, Helena Raurell-Vila, Angela Castela, Jonàs Juan-Mateu, Bobbie-Jo M. Webb-Robertson, Lars Krogvold, Knut Dahl-Jorgensen, Lorella Marselli, Piero Marchetti, Sarah J. Richardson, Noel G. Morgan, Thomas O. Metz, Lorenzo Pasquali, Décio L. Eizirik

المصدر: Nature Communications, Vol 11, Iss 1, Pp 1-17 (2020)

مصطلحات موضوعية: Science

الوصف: The cytokine IFNα is expressed in the islets of individuals with type 1 diabetes and contributes to local inflammation and destruction of beta cells. Here, the authors provide a global multiomics view of IFNα-induced changes in human beta cells at the level of chromatin, mRNA and protein expression.

العلاقة: https://doi.org/10.1038/s41467-020-16327-0Test; https://doaj.org/toc/2041-1723Test; https://doaj.org/article/7ba57ffc94954c2897c0cf413d87e02aTest

الإتاحة: https://doi.org/10.1038/s41467-020-16327-0Test
https://doaj.org/article/7ba57ffc94954c2897c0cf413d87e02aTest

المؤلفون: Mireia Ramos-Rodriguez, Marc Subirana-Granes

الإتاحة: https://doi.org/10.18129/b9.bioc.umi4catsTest
https://bioconductor.org/packages/UMI4CatsTest