High producer variant of lipoprotein lipase may protect from hepatocellular carcinoma in alcohol-associated cirrhosis

Schmalz, Franziska; Fischer, Janett; Innes, Hamish; Buch, Stephan; Möller, Christine; Matz‐Soja, Madlen; Schönfels, Witigo von; Krämer, Benjamin; Langhans, Bettina; Klüners, Alexandra; Soyka, Michael; Stickel, Felix; Nattermann, Jacob; Strassburg, Christian P.; Berg, Thomas; Lutz, Philipp; Nischalke, Hans Dieter

doi:10.1016/j.jhepr.2023.100684

JHEP Reports

2023

DOI: 10.1016/j.jhepr.2023.100684

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High producer variant of lipoprotein lipase may protect from hepatocellular carcinoma in alcohol-associated cirrhosis

Franziska Schmalz¹,

Janett Fischer²,

Hamish Innes³

et al.

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Cited by 4 publications

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“…The Journal of Clinical Investigation J Clin Invest. 2024;134(3):e176345 https://doi.org/10.1172/JCI176345 line variant in TERT and variants of several lipid metabolism-related genes, including MARC1 rs2642438, APOE rs429358, HSD17B13 rs72613567, and LPL rs13702, are associated with reduced risk for cirrhosis or HCC development in patients with ALD(94,(170)(171)(172).…”

mentioning

confidence: 99%

Alcohol-associated liver disease

Mackowiak,

Fu,

Maccioni

et al. 2024

Journal of Clinical Investigation

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mentioning

confidence: 99%

Alcohol-associated liver disease

Mackowiak,

Fu,

Maccioni

et al. 2024

Journal of Clinical Investigation

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Targeting the chromatin remodeling protein BRG1 in liver fibrosis: Mechanism and translational potential

Zhu,

Guo,

Xue

et al. 2024

Life Sciences

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The chromatin remodeling protein BRG1 regulates HSC-myofibroblast differentiation and liver fibrosis

Zhu,

Kang,

Kuai

et al. 2023

Cell Death Dis

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Excessive fibrogenic response in the liver disrupts normal hepatic anatomy and function heralding such end-stage liver diseases as hepatocellular carcinoma and cirrhosis. Myofibroblasts, derived primarily from hepatic stellate cells (HSCs), are the effector of liver fibrosis. In the present study we investigated the mechanism by which Brahma-related gene 1 (BRG1, encoded by Smarca4) regulates HSC-myofibroblast transition and the implication in intervention against liver fibrosis. We report that BRG1 expression was elevated during HSC maturation in cell culture, in animal models, and in human cirrhotic liver biopsy specimens. HSC-specific deletion of BRG1 attenuated liver fibrosis in several different animal models. In addition, BRG1 ablation in myofibroblasts ameliorated liver fibrosis. RNA-seq identified IGFBP5 as a novel target for BRG1. Over-expression of IGFBP5 partially rescued the deficiency in myofibroblast activation when BRG1 was depleted. On the contrary, IGFBP5 knockdown suppressed HSC-myofibroblast transition in vitro and mollified liver fibrosis in mice. Mechanistically, IGFBP5 interacted with Bat3 to stabilize the Bat3-TβR complex and sustain TGF-β signaling. In conclusion, our data provide compelling evidence that BRG1 is a pivotal regulator of liver fibrosis by programming HSC-myofibroblast transition.

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High producer variant of lipoprotein lipase may protect from hepatocellular carcinoma in alcohol-associated cirrhosis

Cited by 4 publications

References 43 publications

Alcohol-associated liver disease

Alcohol-associated liver disease

Targeting the chromatin remodeling protein BRG1 in liver fibrosis: Mechanism and translational potential

The chromatin remodeling protein BRG1 regulates HSC-myofibroblast differentiation and liver fibrosis

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