Suppression of SIRT1/FXR signaling pathway contributes to oleanolic acid-induced liver injury

Liao, Songjie; Fu, Xiaolong; Huang, Jianxiang; Wang, Yi; Lu, Yuan‐Fu; Zhou, Shaoyu

doi:10.1016/j.taap.2023.116509

Cited by 3 publications

(1 citation statement)

References 55 publications

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“…Activation of the SIRT1/HNF1 α /FXR axis may represent a novel therapeutic target for ameliorating ALI and other herb-induced hepatotoxicity ( Liao et al, 2023 ). This is in contrast to the findings of Kemelo et al (2017a) , which demonstrated that SIRT1 negatively regulates HO-1, leading to a reduction in bilirubin production in an LPS-induced mouse model.…”

Section: Survey Methodologymentioning

confidence: 99%

The role of sirtuin1 in liver injury: molecular mechanisms and novel therapeutic target

Wang,

Zhao,

Chen

et al. 2024

PeerJ

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Liver disease is a common and serious threat to human health. The progression of liver diseases is influenced by many physiologic processes, including oxidative stress, inflammation, bile acid metabolism, and autophagy. Various factors lead to the dysfunction of these processes and basing on the different pathogeny, pathology, clinical manifestation, and pathogenesis, liver diseases are grouped into different categories. Specifically, Sirtuin1 (SIRT1), a member of the sirtuin protein family, has been extensively studied in the context of liver injury in recent years and are confirmed the significant role in liver disease. SIRT1 has been found to play a critical role in regulating key processes in liver injury. Further, SIRT1 seems to cause divers outcomes in different types of liver diseases. Recent studies have showed some therapeutic strategies involving modulating SIRT1, which may bring a novel therapeutic target. To elucidate the mechanisms underlying the role of sirtuin1 in liver injury and its potentiality as a therapeutic target, this review outlines the key signaling pathways associated with sirtuin1 and liver injury, and discusses recent advances in therapeutic strategies targeting sirtuin1 in liver diseases.

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Section: Survey Methodologymentioning

confidence: 99%

The role of sirtuin1 in liver injury: molecular mechanisms and novel therapeutic target

Wang,

Zhao,

Chen

et al. 2024

PeerJ

View full text Add to dashboard Cite

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Free fatty acids induce bile acids overproduction and oxidative damage of bovine hepatocytes via inhibiting FXR/SHP signaling

Fang,

Zhou,

et al. 2024

The Journal of Steroid Biochemistry and Molecular Biology

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Activation of Nrf2/HO-1 signaling pathway exacerbates cholestatic liver injury

Wang,

Fu,

Zeng

et al. 2024

Commun Biol

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Nuclear factor erythroid 2-related factor-2 (Nrf2) antioxidant signaling is involved in liver protection, but this generalization overlooks conflicting studies indicating that Nrf2 effects are not necessarily hepatoprotective. The role of Nrf2/heme oxygenase-1 (HO-1) in cholestatic liver injury (CLI) remains poorly defined. Here, we report that Nrf2/HO-1 activation exacerbates liver injury rather than exerting a protective effect in CLI. Inhibiting HO-1 or ameliorating bilirubin transport alleviates liver injury in CLI models. Nrf2 knockout confers hepatoprotection in CLI mice, whereas in non-CLI mice, Nrf2 knockout aggravates liver damage. In the CLI setting, oxidative stress activates Nrf2/HO-1, leads to bilirubin accumulation, and impairs mitochondrial function. High levels of bilirubin reciprocally upregulate the activation of Nrf2 and HO-1, while antioxidant and mitochondrial-targeted SOD2 overexpression attenuate bilirubin toxicity. The expression of Nrf2 and HO-1 is elevated in serum of patients with CLI. These results reveal an unrecognized function of Nrf2 signaling in exacerbating liver injury in cholestatic disease.

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Suppression of SIRT1/FXR signaling pathway contributes to oleanolic acid-induced liver injury

Cited by 3 publications

References 55 publications

The role of sirtuin1 in liver injury: molecular mechanisms and novel therapeutic target

The role of sirtuin1 in liver injury: molecular mechanisms and novel therapeutic target

Free fatty acids induce bile acids overproduction and oxidative damage of bovine hepatocytes via inhibiting FXR/SHP signaling

Activation of Nrf2/HO-1 signaling pathway exacerbates cholestatic liver injury

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