Assessing the combined impact of fatty liver-induced TGF-β1 and LPS-activated macrophages in fibrosis through a novel 3D serial section methodology.

Animals Lipopolysaccharides Transforming Growth Factor beta1 / metabolism Mice Macrophages / metabolism Non-alcoholic Fatty Liver Disease / metabolism Liver Cirrhosis / pathology Diet, High-Fat / adverse effects Male Liver / metabolism Mice, Inbred C57BL Macrophage Activation Imaging, Three-Dimensional / methods Disease Models, Animal Hepatic Stellate Cells / metabolism Interleukin-1beta / metabolism

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
18 May 2024
Historique:
received: 28 12 2023
accepted: 28 04 2024
medline: 19 5 2024
pubmed: 19 5 2024
entrez: 18 5 2024
Statut: epublish

Résumé

Non-alcoholic steatohepatitis (NASH), caused by fat buildup, can lead to liver inflammation and damage. Elucidation of the spatial distribution of fibrotic tissue in the fatty liver in NASH can be immensely useful to understand its pathogenesis. Thus, we developed a novel serial section-3D (SS3D) technique that combines high-resolution image acquisition with 3D construction software, which enabled highly detailed analysis of the mouse liver and extraction and quantification of stained tissues. Moreover, we studied the underexplored mechanism of fibrosis progression in the fatty liver in NASH by subjecting the mice to a high-fat diet (HFD), followed by lipopolysaccharide (LPS) administration. The HFD/LPS (+) group showed extensive fibrosis compared with control; additionally, the area of these fibrotic regions in the HFD/LPS (+) group was almost double that of control using our SS3D technique. LPS administration led to an increase in Tnfα and Il1β mRNA expression and the number of macrophages in the liver. On the other hand, transforming growth factor-β1 (Tgfβ1) mRNA increased in HFD group compared to that of control group without LPS-administration. In addition, COL1A1 levels increased in hepatic stellate cell (HSC)-like XL-2 cells when treated with recombinant TGF-β1, which attenuated with recombinant latency-associated protein (rLAP). This attenuation was rescued with LPS-activated macrophages. Therefore, we demonstrated that fatty liver produced "latent-form" of TGF-β1, which activated by macrophages via inflammatory cytokines such as TNFα and IL1β, resulting in activation of HSCs leading to the production of COL1A1. Moreover, we established the effectiveness of our SS3D technique in creating 3D images of fibrotic tissue, which can be used to study other diseases as well.

Identifiants

DOI: 10.1038/s41598-024-60845-6 PMID: 38762616
pubmed: 38762616
doi: 10.1038/s41598-024-60845-6
pii: 10.1038/s41598-024-60845-6
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

11404

Subventions

Organisme : Japan Science and Technology Agency
ID : JPMJCR19H3

Informations de copyright

© 2024. The Author(s).

Références

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Auteurs

Shiori Ishiyama (S)

Department of Integrated Applied Life Science, Integrated Graduate School of Medicine, Engineering, and Agricultural Sciences, University of Yamanashi, Yamanashi, Japan.

Manabu Hayatsu (M)

Division of Microscopic Anatomy, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.

Taku Toriumi (T)

Department of Anatomy, The Nippon Dental University School of Life Dentistry at Niigata, Niigata, Japan.

Hiromasa Tsuda (H)

Department of Biochemistry, Nihon University School of Dentistry, Tokyo, Japan.

Keisuke Watanabe (K)

Division of Gross Anatomy and Morphogenesis, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.

Hirotake Kasai (H)

Department of Microbiology, Faculty of Medicine, Graduate Faculty of Interdisciplinary Research, University of Yamanashi, Yamanashi, Japan.

Satoshi Kishigami (S)

Department of Integrated Applied Life Science, Integrated Graduate School of Medicine, Engineering, and Agricultural Sciences, University of Yamanashi, Yamanashi, Japan.
Center for Advanced Assisted Reproductive Technologies, University of Yamanashi, Yamanashi, Japan.

Kazuki Mochizuki (K)

Department of Integrated Applied Life Science, Integrated Graduate School of Medicine, Engineering, and Agricultural Sciences, University of Yamanashi, Yamanashi, Japan. mochizukik@yamanashi.ac.jp.

Yoshikazu Mikami (Y)

Division of Microscopic Anatomy, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan. mikami-yoshikazu@med.niigata-u.ac.jp.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Assessing the combined impact of fatty...
questionsmedicales.fr › Facteurs biologiques › Toxines biologiques › Toxines bactériennes › Endotoxines › Lipopolysaccharides › Assessing the combined impact of fatty...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Protéines de la superfamille du TGF bêta › Facteur de croissance transformant bêta › Facteur de croissance transformant bêta-1 › Assessing the combined impact of fatty...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Assessing the combined impact of fatty...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Phagocytes › Macrophages › Assessing the combined impact of fatty...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies du foie › Stéatose hépatique › Stéatose hépatique non alcoolique › Assessing the combined impact of fatty...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Fibrose › Cirrhose du foie › Assessing the combined impact of fatty...
questionsmedicales.fr › Phénomènes physiologiques › Alimentation et nutrition › Phénomènes physiologiques nutritionnels › Régime alimentaire › Alimentation riche en graisse › Assessing the combined impact of fatty...
questionsmedicales.fr › Système digestif › Foie › Assessing the combined impact of fatty...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Assessing the combined impact of fatty...
questionsmedicales.fr › Phénomènes du système immunitaire › Cytotoxicité immunologique › Activation des macrophages › Assessing the combined impact of fatty...
questionsmedicales.fr › Sciences de l'information › Méthodologies informatiques › Traitement d'image par ordinateur › Imagerie tridimensionnelle › Assessing the combined impact of fatty...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Assessing the combined impact of fatty...
questionsmedicales.fr › Cellules › Cellules étoilées du foie › Assessing the combined impact of fatty...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Monokines › Interleukine-1 › Interleukine-1 bêta › Assessing the combined impact of fatty...