2021
DOI: 10.1038/s41598-021-99958-7
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Loss of hepatic Flcn protects against fibrosis and inflammation by activating autophagy pathways

Abstract: Non-alcoholic fatty liver disease (NAFLD) is the most frequent liver disease worldwide and can progress to non-alcoholic steatohepatitis (NASH), which is characterized by triglyceride accumulation, inflammation, and fibrosis. No pharmacological agents are currently approved to treat these conditions, but it is clear now that modulation of lipid synthesis and autophagy are key biological mechanisms that could help reduce or prevent these liver diseases. The folliculin (FLCN) protein has been recently identified… Show more

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Cited by 7 publications
(5 citation statements)
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“…The past few years have seen a paradigm shift in understanding how the MiT-TFE family of transcription factors is regulated downstream of mTORC1 in a uniquely FLCN-and RagC GDP -dependent manner (10,11). Numerous studies corroborate the discovery of a "noncanonical" mTORC1 pathway that specifically regulates MiT-TFE transcription factors (12,21,(35)(36)(37)(38). The new knowledge of FLCN structural mechanism provided by the AFC structure can potentially be exploited for therapeutic benefit.…”
Section: Discussionmentioning
confidence: 99%
“…The past few years have seen a paradigm shift in understanding how the MiT-TFE family of transcription factors is regulated downstream of mTORC1 in a uniquely FLCN-and RagC GDP -dependent manner (10,11). Numerous studies corroborate the discovery of a "noncanonical" mTORC1 pathway that specifically regulates MiT-TFE transcription factors (12,21,(35)(36)(37)(38). The new knowledge of FLCN structural mechanism provided by the AFC structure can potentially be exploited for therapeutic benefit.…”
Section: Discussionmentioning
confidence: 99%
“…Notably, cilostazol significantly dampened the ratio of PLT-RBCs to total RBCs in a dose-dependent manner ( Figure 4 G). RBC-PLT binding induces the Fas pathway in both RBCs and PLTs resulting in phosphatidylserine exposure [ 21 ]. Thus, we next examined RBC-PLT binding by Annexin-V flow cytometry.…”
Section: Resultsmentioning
confidence: 99%
“…The past few years have seen a paradigm shift in understanding how the MiTF family of transcription factors is regulated downstream of mTORC1 in a uniquely FLCN and RagC GDPdependent manner (10,11). Numerous studies corroborate the discovery of a "non-canonical" mTORC1 pathway that specifically regulates MiT-TFE transcription factors (12,21,(35)(36)(37)(38). The new knowledge of FLCN structural mechanism provided by the AFC structure can potentially be exploited for therapeutic benefit.…”
Section: Discussionmentioning
confidence: 99%
“…The past few years have seen a paradigm shift in understanding how the MiTF family of transcription factors is regulated downstream of mTORC1 in a uniquely FLCN and RagC GDP -dependent manner ( 8, 9, 18, 19, 21, 32, 33 ). The new knowledge of FLCN structural mechanism provided by the AFC structure can potentially be exploited for therapeutic benefit.…”
Section: Main Textmentioning
confidence: 99%