Neuregulin1 ameliorates metabolic dysfunction-associated fatty liver disease via the ERK/SIRT1 signaling pathways
Abstract Background Neuregulin (NRG) family is involved in energy metabolism, among which NRG1 is a neuregulin proved to play a protective role in MAFLD cells. But the presice echanism has not been fully illustrated. This study aimed to investigate the role of NRG1 via the ERK/SIRT1 signaling in the...
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BMC
2025-01-01
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| Series: | BMC Gastroenterology |
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| Online Access: | https://doi.org/10.1186/s12876-025-03632-5 |
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| author | Chengan Xu Shouhao Wang Di Meng Mingshan Wang Rong Yan Yining Dai |
| author_facet | Chengan Xu Shouhao Wang Di Meng Mingshan Wang Rong Yan Yining Dai |
| author_sort | Chengan Xu |
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| description | Abstract Background Neuregulin (NRG) family is involved in energy metabolism, among which NRG1 is a neuregulin proved to play a protective role in MAFLD cells. But the presice echanism has not been fully illustrated. This study aimed to investigate the role of NRG1 via the ERK/SIRT1 signaling in the pathogenesis of MAFLD. Methods C57BL/6 mice were fed with high-fat diet for 8 weeks, and then injected with NRG1 (0.3 mg/kg/d) and PD98059 (0.3 mg/kg/d) via tail vein for 5 weeks. HepG2 cells induced by oleic acid and palmitic acid were treated with 20ng/mL NRG1 and 10µmol/L PD98059. The changes of histopathological, biochemical indexes, inflammatory factors, lipid metabolism, apoptosis and autophagy parameters were measured. Results The expressions of NRG1 in MAFLD cell and animal models were significantly lower than that in the control group. After the intervention of ERK inhibitor PD98059, the expression of NRG1 decreased significantly in vivo, but no significant change was observed in vitro. Moreover, NRG1 ameliorated hepatic steatosis, enhanced cell viability, reduced cell apoptosis, and attenuated liver injury both in vitro and in vivo. After NRG1 intervention, the expressions of ERBB2, ERBB3, p-ERK1/2, SIRT1 and p-FOXO1 as well as the LC3II/I ratio in MAFLD cells and liver tissues of MAFLD mice were significantly increased, while the expression of SREBP1c was decreased. The aforementioned therapeutic effect of NRG1 was lost after the intervention of PD98059. Conclusion NRG1 might play a protective role in the pathogenesis of MAFLD by activating the downstream ERK1/2 through ErbB2-ErbB3, which promotes the expression of SIRT1 and autophagy markers. This study might indicate a new therapeutic strategy for MAFLD. |
| format | Article |
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| institution | Kabale University |
| issn | 1471-230X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | BMC Gastroenterology |
| spelling | doaj-art-0c65a91743214b34a5292e74f9502e9a2025-02-02T12:27:17ZengBMCBMC Gastroenterology1471-230X2025-01-012511910.1186/s12876-025-03632-5Neuregulin1 ameliorates metabolic dysfunction-associated fatty liver disease via the ERK/SIRT1 signaling pathwaysChengan Xu0Shouhao Wang1Di Meng2Mingshan Wang3Rong Yan4Yining Dai5Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College)Hepatology Diagnosis and Treatment Center, Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang UniversityCenter for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College)Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College)Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College)Abstract Background Neuregulin (NRG) family is involved in energy metabolism, among which NRG1 is a neuregulin proved to play a protective role in MAFLD cells. But the presice echanism has not been fully illustrated. This study aimed to investigate the role of NRG1 via the ERK/SIRT1 signaling in the pathogenesis of MAFLD. Methods C57BL/6 mice were fed with high-fat diet for 8 weeks, and then injected with NRG1 (0.3 mg/kg/d) and PD98059 (0.3 mg/kg/d) via tail vein for 5 weeks. HepG2 cells induced by oleic acid and palmitic acid were treated with 20ng/mL NRG1 and 10µmol/L PD98059. The changes of histopathological, biochemical indexes, inflammatory factors, lipid metabolism, apoptosis and autophagy parameters were measured. Results The expressions of NRG1 in MAFLD cell and animal models were significantly lower than that in the control group. After the intervention of ERK inhibitor PD98059, the expression of NRG1 decreased significantly in vivo, but no significant change was observed in vitro. Moreover, NRG1 ameliorated hepatic steatosis, enhanced cell viability, reduced cell apoptosis, and attenuated liver injury both in vitro and in vivo. After NRG1 intervention, the expressions of ERBB2, ERBB3, p-ERK1/2, SIRT1 and p-FOXO1 as well as the LC3II/I ratio in MAFLD cells and liver tissues of MAFLD mice were significantly increased, while the expression of SREBP1c was decreased. The aforementioned therapeutic effect of NRG1 was lost after the intervention of PD98059. Conclusion NRG1 might play a protective role in the pathogenesis of MAFLD by activating the downstream ERK1/2 through ErbB2-ErbB3, which promotes the expression of SIRT1 and autophagy markers. This study might indicate a new therapeutic strategy for MAFLD.https://doi.org/10.1186/s12876-025-03632-5Metabolic dysfunction-associated fatty liver diseaseNeuregulin 1ERKSIRT1Autophagy |
| spellingShingle | Chengan Xu Shouhao Wang Di Meng Mingshan Wang Rong Yan Yining Dai Neuregulin1 ameliorates metabolic dysfunction-associated fatty liver disease via the ERK/SIRT1 signaling pathways BMC Gastroenterology Metabolic dysfunction-associated fatty liver disease Neuregulin 1 ERK SIRT1 Autophagy |
| title | Neuregulin1 ameliorates metabolic dysfunction-associated fatty liver disease via the ERK/SIRT1 signaling pathways |
| title_full | Neuregulin1 ameliorates metabolic dysfunction-associated fatty liver disease via the ERK/SIRT1 signaling pathways |
| title_fullStr | Neuregulin1 ameliorates metabolic dysfunction-associated fatty liver disease via the ERK/SIRT1 signaling pathways |
| title_full_unstemmed | Neuregulin1 ameliorates metabolic dysfunction-associated fatty liver disease via the ERK/SIRT1 signaling pathways |
| title_short | Neuregulin1 ameliorates metabolic dysfunction-associated fatty liver disease via the ERK/SIRT1 signaling pathways |
| title_sort | neuregulin1 ameliorates metabolic dysfunction associated fatty liver disease via the erk sirt1 signaling pathways |
| topic | Metabolic dysfunction-associated fatty liver disease Neuregulin 1 ERK SIRT1 Autophagy |
| url | https://doi.org/10.1186/s12876-025-03632-5 |
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