دورية أكاديمية
Regulation of the macrophage-hepatic stellate cell interaction by targeting macrophage peroxisome proliferator-activated receptor gamma to prevent non-alcoholic steatohepatitis progression in mice.
| العنوان: | Regulation of the macrophage-hepatic stellate cell interaction by targeting macrophage peroxisome proliferator-activated receptor gamma to prevent non-alcoholic steatohepatitis progression in mice. |
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| المؤلفون: | Ni XX; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; NHC Key Laboratory of Digestive Diseases; NHC Key Laboratory of Digestive Diseases; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China., Ji PX; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; NHC Key Laboratory of Digestive Diseases; NHC Key Laboratory of Digestive Diseases; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China., Chen YX; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; NHC Key Laboratory of Digestive Diseases; NHC Key Laboratory of Digestive Diseases; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China., Li XY; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; NHC Key Laboratory of Digestive Diseases; NHC Key Laboratory of Digestive Diseases; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China., Sheng L; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; NHC Key Laboratory of Digestive Diseases; NHC Key Laboratory of Digestive Diseases; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China., Lian M; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; NHC Key Laboratory of Digestive Diseases; NHC Key Laboratory of Digestive Diseases; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China., Guo CJ; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; NHC Key Laboratory of Digestive Diseases; NHC Key Laboratory of Digestive Diseases; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China., Hua J; Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; NHC Key Laboratory of Digestive Diseases; NHC Key Laboratory of Digestive Diseases; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. |
| المصدر: | Liver international : official journal of the International Association for the Study of the Liver [Liver Int] 2022 Dec; Vol. 42 (12), pp. 2696-2712. Date of Electronic Publication: 2022 Oct 11. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Wiley-Blackwell Country of Publication: United States NLM ID: 101160857 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1478-3231 (Electronic) Linking ISSN: 14783223 NLM ISO Abbreviation: Liver Int Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Malden, MA : Wiley-Blackwell Original Publication: Oxford, UK : Blackwell Munksgaard, c2003- |
| مواضيع طبية MeSH: | Hepatic Stellate Cells*/metabolism , Non-alcoholic Fatty Liver Disease*/prevention & control , Non-alcoholic Fatty Liver Disease*/metabolism, Mice ; Animals ; PPAR gamma/metabolism ; Culture Media, Conditioned/metabolism ; Mice, Inbred C57BL ; Macrophages/metabolism ; Liver/metabolism ; Liver Cirrhosis/pathology ; Inflammation/pathology ; Methionine/metabolism |
| مستخلص: | Background & Aims: Macrophages display remarkable plasticity and can interact with surrounding cells to affect hepatic immunity and tissue remodelling during the progression of liver diseases. Peroxisome proliferator-activated receptor gamma (PPARγ) plays a critical role in macrophage maturation, polarization and metabolism. In this study, we investigated the role of PPARγ in macrophage-hepatic stellate cell (HSC) interaction during non-alcoholic steatohepatitis (NASH) development. Methods: Wild-type, Pparg fl/fl and Pparg ΔLyz2 mice were fed a methionine- and choline-deficient (MCD) diet to induce NASH. Depletion of macrophages was performed using an injection of gadolinium chloride intraperitoneally. PPARγ-overexpressing or PPARγ-knockout macrophages were stimulated with saturated fatty acid (SFA) and cocultured with HSCs in a conditioned medium or the transwell coculture system. Results: Depletion of macrophages inhibited HSC activation and ameliorated NASH progression in MCD diet-fed mice. Coculturing HSCs with macrophages or culturing HSCs in a macrophage-conditioned medium-facilitated HSC activation, and this effect was magnified when macrophages were metabolically activated by SFA. Moreover, the absence of PPARγ in macrophages enhanced metabolic activation, promoting the migration and activation of HSCs through IL-1β and CCL2. In contrast, overexpression of PPARγ in macrophages obtained the opposite effects. In vivo, macrophage-specific PPARγ knockout affected the phenotype of hepatic macrophages and HSCs, involving the MAPK and NLRP3/caspase-1/IL-1β signalling pathways. Infiltrating hepatic monocyte-derived macrophages became the predominant macrophages in NASH liver, especially in Pparg ΔLyz2 mice, paralleling with aggravated inflammation and fibrosis. Conclusions: Regulating macrophage PPARγ affected the metabolic activation of macrophages and their interaction with HSCs. Macrophage-specific PPARγ may be an attractive therapeutic target for protecting against NASH-associated inflammation and fibrosis. (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.) |
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| فهرسة مساهمة: | Keywords: PPAR gamma; fibrosis; hepatic stellate cells; inflammation; macrophages; non-alcoholic fatty liver disease |
| المشرفين على المادة: | 0 (PPAR gamma) 0 (Culture Media, Conditioned) AE28F7PNPL (Methionine) |
| تواريخ الأحداث: | Date Created: 20220927 Date Completed: 20221124 Latest Revision: 20221216 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1111/liv.15441 |
| PMID: | 36165186 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1478-3231 |
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| DOI: | 10.1111/liv.15441 |