Inhibition of miR-431-5p attenuated liver apoptosis through KLF15/p53 signal pathway in S100 induced autoimmune hepatitis mice

Tu, Yulu; Chen, Runsheng; Pan, Tongtong; Chen, Zhengkang; Xu, Jie; Jin, Lanling; Sheng, Lina; Jin, Xiaozhi; Wang, Xiaodong; Lan, Xiaolin; Ge, Yuli; Sun, Honghong; Chen, Yongping

doi:10.1016/j.lfs.2021.119698

Cited by 10 publications

(5 citation statements)

References 40 publications

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“…Activation of the apoptotic machinery is divided into an intrinsic mitochondria-dependent mediated pathway and an extrinsic death receptor-dependent triggered pathway [13,14]. Apoptosis is reportedly involved in the pathogenesis of acute liver injury, hepatitis, and liver cancer [15][16][17]. During reperfusion, TNF-α and other mediators activate many proteins involved in apoptosis, such as the protease caspase-3, caspase-9, and bax [18,19].…”

Section: Introductionmentioning

confidence: 99%

Cordycepin Protects against Hepatic Ischemia/Reperfusion Injury via Inhibiting MAPK/NF-κB Pathway

Ding

WenjuanYang

Jiang

et al. 2022

Mediators of Inflammation

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Hepatic ischemia/reperfusion injury (HIRI) is a common complication of liver surgery requiring hepatic disconnection, such as hepatectomy and liver transplantation. The aim of this study was to investigate the effects of cordycepin on HIRI and to elucidate the underlying mechanisms. Balb/c mice were randomly divided into six groups: a normal control group, sham group, H-cordycepin group, HIRI group, L-cordycepin (25 mg/kg) + HIRI group, and H-cordycepin (50 mg/kg) + HIRI group. Mice were subjected to I/R, and cordycepin was intragastrically administered for seven consecutive days before surgery. Orbital blood and liver specimens were collected at 6 and 24 h after HIRI. Serum levels of ALT and AST were decreased in the cordycepin pretreatment groups. Notably, cordycepin attenuated the inflammatory response and the production of proapoptosis proteins, while increasing expression of antiapoptosis proteins and decreasing expression of autophagy-linked proteins. Furthermore, cordycepin inhibited activation of the MAPK/NF-κB signaling pathway. Collectively, these results indicate that cordycepin pretreatment ameliorated hepatocyte injury caused by HIRI. As compared with the HIRI group, cordycepin pretreatment mitigated the inflammatory response and inhibited apoptosis and autophagy via regulation of the MAPK/NF-κB signaling pathway.

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Section: Introductionmentioning

confidence: 99%

Cordycepin Protects against Hepatic Ischemia/Reperfusion Injury via Inhibiting MAPK/NF-κB Pathway

Ding

WenjuanYang

Jiang

et al. 2022

Mediators of Inflammation

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“…Overexpression of KLF15 significantly inhibited the apoptosis and inflammation levels of liver via p38MAPK/ERK1/2 pathway (Tian et al, 2020). Another study also showed that knockdown of KLF15 promoted Bax expression, but BCL-2 level was inhibited by activating p53 pathway in LPS induced AML-12 cells (Tu et al, 2021). These results indicate that KLF15 may improve ALI by regulating apoptosis.…”

Section: Klf15 and Endobiotic And Xenobiotic Metabolism (Exm)mentioning

confidence: 78%

“…A recent study showed that downregulation of miR-431-5p inhibited apoptosis via KLF15/ p53 pathway in S100 induced AIH mice and KLF15 inhibition abolished this event. (Tu et al, 2021) (Figure 5). Although few studies focus on the role of KLF in AIH, current evidence tentatively suggests that KLF15 is a promising target in treating AIH.…”

Section: Klf15 and Autoimmune Hepatitis (Aih)mentioning

confidence: 99%

Krüppel-like factor 15 in liver diseases: Insights into metabolic reprogramming

Chen

Li²,

Du³

2023

Front. Pharmacol.

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Liver diseases, characterized by metabolic disorder, have become a global public health problem with high morbidity and mortality. Krüppel-like factor 15 (KLF15) is a zinc-finger transcription factor mainly enriched in liver. Increasing evidence suggests that hepatic KLF15 is activated rapidly during fasting, and contributes to the regulation of gluconeogenesis, lipid, amino acid catabolism, bile acids, endobiotic and xenobiotic metabolism. This review summarizes the latest advances of KLF15 in metabolic reprogramming, and explore the function of KLF15 in acute liver injury, hepatitis B virus, and autoimmune hepatitis. which aims to evaluate the potential of KLF15 as a therapeutic target and prognostic biomarker for liver diseases.

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“…Although AIH is more likely to occur in women, male C57BL/C6 mice have the strongest susceptibility to AIH based on previous work on multiple mouse models, with such susceptibility observed in almost all of the established models [ 10 ]. Previous AIH models constructed using S100 also mostly used male C57BL/6J [ 32 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

Umbilical Cord-Derived Mesenchymal Stem Cells Attenuate S100-Induced Autoimmune Hepatitis via Modulating Th1 and Th17 Cell Responses in Mice

Wei,

Cheng,

Luo

et al. 2023

Stem Cells International

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Currently, the first-line treatment for autoimmune hepatitis (AIH) is still the combination of glucocorticoids or immunosuppressants. However, hormone and immunosuppressive therapy can cause serious side effects, such as Cushing syndrome and bone marrow suppression. Previous studies reported on the applicability and safety of mesenchymal stem cells (MSCs) to ameliorate liver inflammation and fibrosis. However, the characteristics of MSCs sources directly contribute to the different conclusions on the mechanisms underlying MSC-mediated immunoregulation. Bone marrow-derived MSCs can exert an immunosuppression effect to ameliorate the S100-induced AIH model by inhibiting several proinflammatory cytokines and upregulating of PD-L1 in liver tissue. It is not clear whether human umbilical cord-derived MSCs (hUC-MSCs) could directly inhibit liver inflammation and ultimately alleviate the dysfunction of hepatocytes in the AIH model. First, hUC-MSCs were extracted from umbilical cord tissue, and the basic biological properties and multilineage differentiation potential were examined. Second, 1 × 106 hUC-MSCs were administered intravenously to AIH mice. At the peak of the disease, serum levels of alanine aminotransferase and aspartate aminotransferase and pathologic damage to liver tissue were measured to evaluate liver function and degree of inflammation. We also observed that the infiltration of CD4+ T cells in the liver was significantly reduced. Furthermore, the frequency of the splenic IFNγ- and IL-17A- producing CD4+ T cells were also significantly decreased, while we only observed an increasing trend in Treg cells in liver tissue. Third, an RNA sequencing analysis of liver tissue was performed, which showed that in the UC-MSC-treated group, the transcriptional profiles of inflammation-related signaling pathways were significantly negatively regulated compared to those of phosphate-buffered saline-treated mice. Collectively, these findings indicated the potential of hUC-MSC to suppress immune responses in immune anomaly mediated liver disease, thus offering a potential clinical option to improve AIH.

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Inhibition of miR-431-5p attenuated liver apoptosis through KLF15/p53 signal pathway in S100 induced autoimmune hepatitis mice

Cited by 10 publications

References 40 publications

Cordycepin Protects against Hepatic Ischemia/Reperfusion Injury via Inhibiting MAPK/NF-κB Pathway

Cordycepin Protects against Hepatic Ischemia/Reperfusion Injury via Inhibiting MAPK/NF-κB Pathway

Krüppel-like factor 15 in liver diseases: Insights into metabolic reprogramming

Umbilical Cord-Derived Mesenchymal Stem Cells Attenuate S100-Induced Autoimmune Hepatitis via Modulating Th1 and Th17 Cell Responses in Mice

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