Astaxanthin prevents TGFβ1-induced pro-fibrogenic gene expression by inhibiting Smad3 activation in hepatic stellate cells

Yang, Yue; Kim, Bohkyung; Park, Youngki; Koo, Sung I.; Lee, Ji-Young

doi:10.1016/j.bbagen.2014.10.014

Cited by 88 publications

(71 citation statements)

References 61 publications

(71 reference statements)

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“…Furthermore, astaxanthin is 100- to 500-fold more effective than vitamin E in inhibiting lipid peroxidation and it inhibits carbon tetrachloride-induced lipid peroxidation in a rat’s liver. Astaxanthin also prevents the activation of hepatic stellate cells, thereby suppressing the up-regulation of fibrogenic genes by blocking transforming growth factor-β/Smad3 signaling [87,88,89]. In addition, it interferes with diet-induced obesity and hepatic lipid accumulation in mice, and ameliorates oxidative-stress-induced insulin resistance through the enhancement of insulin signaling and the inhibition of pro-inflammatory signaling [90,91,92].…”

Section: Antioxidant Carotenoids For the Treatment Of Nafldmentioning

confidence: 99%

Nonalcoholic Fatty Liver Disease and Insulin Resistance: New Insights and Potential New Treatments

2017

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Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver disorders worldwide. It is associated with clinical states such as obesity, insulin resistance, and type 2 diabetes, and covers a wide range of liver changes, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma. Metabolic disorders, such as lipid accumulation, insulin resistance, and inflammation, have been implicated in the pathogenesis of NAFLD, but the underlying mechanisms, including those that drive disease progression, are not fully understood. Both innate and recruited immune cells mediate the development of insulin resistance and NASH. Therefore, modifying the polarization of resident and recruited macrophage/Kupffer cells is expected to lead to new therapeutic strategies in NAFLD. Oxidative stress is also pivotal for the progression of NASH, which has generated interest in carotenoids as potent micronutrient antioxidants in the treatment of NAFLD. In addition to their antioxidative function, carotenoids regulate macrophage/Kupffer cell polarization and thereby prevent NASH progression. In this review, we summarize the molecular mechanisms involved in the pathogenesis of NAFLD, including macrophage/Kupffer cell polarization, and disturbed hepatic function in NAFLD. We also discuss dietary antioxidants, such as β-cryptoxanthin and astaxanthin, that may be effective in the prevention or treatment of NAFLD.

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Section: Antioxidant Carotenoids For the Treatment Of Nafldmentioning

confidence: 99%

Nonalcoholic Fatty Liver Disease and Insulin Resistance: New Insights and Potential New Treatments

2017

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“…The final published version may differ from this proof. ROS inhibitors such as astaxanthin were shown to reduce fibrotic development through SMAD/TGFβ signaling (60). The intended vascular structure may also be designed with regard for the expected oxygen tension in situ.…”

Section: Page 8 Of 28mentioning

confidence: 99%

Environmental Influences on Endothelial to Mesenchymal Transition in Developing Implanted Cardiovascular Tissue-Engineered Grafts

Muylaert

Jong

Slaats

et al. 2016

Tissue Engineering Part B: Reviews

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Tissue-engineered grafts for cardiovascular structures experience biochemical stimuli and mechanical forces that influence tissue development after implantation such as the immunological response, oxidative stress, hemodynamic shear stress, and mechanical strain. Endothelial cells are a cell source of major interest in vascular tissue engineering because of their ability to form a luminal antithrombotic monolayer. In addition, through their ability to undergo endothelial to mesenchymal transition (EndMT), endothelial cells may yield a cell type capable of increased production and remodeling of the extracellular matrix (ECM). ECM is of major importance to the mechanical function of all cardiovascular structures. Tissue engineering approaches may employ EndMT to recapitulate, in part, the embryonic development of cardiovascular structures. Improved understanding of how the environment of an implanted graft could influence EndMT in endothelial cells may lead to novel tissue engineering strategies. This review presents an overview of biochemical and mechanical stimuli capable of influencing EndMT, discusses the influence of these stimuli as found in the direct environment of cardiovascular grafts, and discusses approaches to employ EndMT in tissue-engineered constructs.

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“…Astaxanthin (ASTX), a xanthophyll carotenoid, is shown to have an antioxidant capacity greater than that of other carotenoids, such as α‐carotene, lycopene (LY), zeaxanthin (ZEAX), and lutein (LT) (Goto et al, ; McNulty et al, ; Palozza and Krinsky, ). We previously demonstrated that ASTX has an anti‐fibrogenic effect in LX‐2 cells, a human HSC cell line, as well as primary human and mouse HSC (Yang et al, , , ). In vivo studies have also shown that ASTX exerts an anti‐fibrogenic effect in the liver of mice with fibrosis induced by carbon tetrachloride (CCl 4 ) or bile duct ligation (BDL) (Shen et al, ) or high‐fat diets (Kim et al, ).…”

Section: Introductionmentioning

confidence: 99%

Comparison of Carotenoids for Their Antifibrogenic Effects in Hepatic Stellate Cells

Bae

Kim

Kang

et al. 2019

Lipids

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Hepatic stellate cells (HSC) have an important role in the development of liver fibrosis by producing extracellular matrix proteins when they are activated upon liver injury. We previously demonstrated that astaxanthin (ASTX), a xanthophyll carotenoid, attenuates HSC activation. The objective of this study was to compare the anti‐fibrogenic effects of ASTX with those of other common carotenoids. LX‐2 cells, a human HSC cell line, were treated with ASTX, lycopene, lutein (LT), zeaxanthin, or canthaxanthin, to measure messenger RNA (mRNA) and protein expression of pro‐fibrogenic genes. Pro‐fibrogenic gene expressions were also measured in ASTX‐ or LT‐treated primary mouse HSC. To determine the underlying mechanisms of the anti‐fibrogenic effect of ASTX and LT, SMA‐related and MAD‐related protein 3 (SMAD3) pathways and the accumulation of reactive oxygen species (ROS) were measured in LX‐2 cells. Among five carotenoids tested, ASTX and LT attenuated HSC activation in LX‐2 cells by reducing the mRNA and protein levels of pro‐fibrogenic genes, such as smooth muscle α actin and procollagen type I α1 (COL1A1). In addition, both ASTX and LT significantly decreased the expression of pro‐fibrogenic genes, including COL1A1, COL3A1, and COL6A1, in activated primary mouse HSC, with ASTX being more potent than LT. The anti‐fibrogenic effect of ASTX was mediated by inhibiting the phosphorylation of SMAD3 and cellular ROS accumulation, while LT only prevented the accumulation of ROS in LX‐2 cells. In conclusion, ASTX showed the most potent anti‐fibrogenic effect among the five carotenoids via inhibition of SMAD3 phosphorylation and cellular ROS accumulation while LT only prevented ROS levels in HSC.

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Astaxanthin prevents TGFβ1-induced pro-fibrogenic gene expression by inhibiting Smad3 activation in hepatic stellate cells

Cited by 88 publications

References 61 publications

Nonalcoholic Fatty Liver Disease and Insulin Resistance: New Insights and Potential New Treatments

Nonalcoholic Fatty Liver Disease and Insulin Resistance: New Insights and Potential New Treatments

Environmental Influences on Endothelial to Mesenchymal Transition in Developing Implanted Cardiovascular Tissue-Engineered Grafts

Comparison of Carotenoids for Their Antifibrogenic Effects in Hepatic Stellate Cells

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