Fatty acid binding protein-4 (FABP4) is a hypoxia inducible gene that sensitizes mice to liver ischemia/reperfusion injury

Hu, Bang; Guo, Yan; Garbacz, Wojciech G.; Jiang, Mengxi; Xu, Meishu; Huang, Hai; Tsung, Allan; Billiar, Timothy R.; Ramakrishnan, S; Shah, Yatrik M.; Lam, Karen Siu Ling; Huang, Min; Xie, Wen

doi:10.1016/j.jhep.2015.05.030

Cited by 47 publications

(45 citation statements)

References 41 publications

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“…Importantly, we show that the DOPC nanoliposomes containing a miR-409-3p mimic effectively reduce tumor burden and metastasis in vivo. Hypoxia has been linked with ovarian cancer progression 48 , 49 . However, the exact role of hypoxia in tumor metastatic patterns was not well understood.…”

Section: Discussionmentioning

confidence: 99%

FABP4 as a key determinant of metastatic potential of ovarian cancer

et al. 2018

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The standard treatment for high-grade serous ovarian cancer is primary debulking surgery followed by chemotherapy. The extent of metastasis and invasive potential of lesions can influence the outcome of these primary surgeries. Here, we explored the underlying mechanisms that could increase metastatic potential in ovarian cancer. We discovered that FABP4 (fatty acid binding protein) can substantially increase the metastatic potential of cancer cells. We also found that miR-409-3p regulates FABP4 in ovarian cancer cells and that hypoxia decreases miR-409-3p levels. Treatment with DOPC nanoliposomes containing either miR-409-3p mimic or FABP4 siRNA inhibited tumor progression in mouse models. With RPPA and metabolite arrays, we found that FABP4 regulates pathways associated with metastasis and affects metabolic pathways in ovarian cancer cells. Collectively, these findings demonstrate that FABP4 is functionally responsible for aggressive patterns of disease that likely contribute to poor prognosis in ovarian cancer.

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Section: Discussionmentioning

confidence: 99%

FABP4 as a key determinant of metastatic potential of ovarian cancer

et al. 2018

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“…FABP4 is an inducible gene, and inflammatory mediators, such as Th2 cytokines, HIF-1␣, and LPS, are known to induce expression of this protein in other cell types (33,44,59). In addition, FABP4 has been shown to be induced by growth factors such as VEGF in endothelial cells and to function as a regulator of cell proliferation and airway angiogenesis (23).…”

Section: Discussionmentioning

confidence: 99%

FABP4 regulates eosinophil recruitment and activation in allergic airway inflammation

Ge¹,

Baştan²,

Dileepan³

et al. 2018

American Journal of Physiology-Lung Cellular and Molecular Phys

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Fatty acid binding protein 4 (FABP4), a member of a family of lipid-binding proteins, is known to play a role in inflammation by virtue of its ability to regulate intracellular events such as lipid fluxes and signaling. Studies have indicated a proinflammatory role for FABP4 in allergic asthma although its expression and function in eosinophils, the predominant inflammatory cells recruited to allergic airways, were not investigated. We examined expression of FABP4 in murine eosinophils and its role in regulating cell recruitment in vitro as well as in cockroach antigen (CRA)-induced allergic airway inflammation. CRA exposure led to airway recruitment of FABP4-expressing inflammatory cells, specifically eosinophils, in wild-type (WT) mice. FABP4 expression in eosinophils was induced by TNF-α as well as IL-4 and IL-13. FABP4-deficient eosinophils exhibited markedly decreased cell spreading/formation of leading edges on vascular cell adhesion molecule-1 and significantly decreased adhesion to intercellular adhesion molecule-1 associated with reduced β2-integrin expression relative to WT cells. Furthermore, FABP4-deficient eosinophils exhibited decreased migration, F-actin polymerization, calcium flux, and ERK(1/2) phosphorylation in response to eotaxin-1. In vivo, CRA-challenged FABP4-deficient mice exhibited attenuated eosinophilia and significantly reduced airway inflammation (improved airway reactivity, lower IL-5, IL-13, TNF-α, and cysteinyl leukotriene C4 levels, decreased airway structural changes) compared with WT mice. In conclusion, expression of FABP4 in eosinophils is induced during conditions of inflammation and plays a proinflammatory role in the development of allergic asthma by promoting eosinophil adhesion and migration and contributing to the development of various aspects of airway inflammation.

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“…Elevated serum FABP4 is associated with carotid atherosclerosis, plaque instability, and cardiovascular disease . In addition, oxidative stress and inflammation in the liver are markedly induced by an increase in FABP4 expression, and overexpression of FABP4 in the liver is a source of organ damage , because FABP4 is expressed in activated macrophages, which then induces an inflammatory response. Treatment with BTpow or BText did not affect the FABP4 level in plasma (Fig.…”

Section: Discussionmentioning

confidence: 99%

Anti‐obesity and anti‐inflammatory effects of peroxisome proliferator activated receptor‐γ induced by bofutsushosan powder versus extract

Kobayashi

Saito

Yumita

et al. 2017

Traditional & Kampo Medicine

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Aim: Bofutsushosan (BT) has been used to treat systemic inflammatory diseases, including obesity, according to an original Chinese prescription book written in 1172. The '-san' suffix of 'Bofutsushosan' means that BT is prescribed as a pulverized crude drug. Peroxisome proliferator-activated receptor (PPAR)γ is known to play a pivotal role in adipocyte differentiation and to downregulate the transcription of adipocytokine genes leading to an inflammatory response. Given that the 'san' formulation is important for the anti-inflammation effect, we compared the anti-obesity and anti-inflammatory effects of PPARγ induced by BT powder with those by BT extract. Methods: The PPARγ agonistic activity of the separate crude BT drug components was measured on enzyme-linked immunosorbent assay (ELISA). For in vivo studies, male mice of the C57BL/6 strain were fed a high-fat diet containing 6.4% BT extract or BT powder for 65 days. Results: Water extract prepared from the BT components Saposhnikoviae Radix, Zingiberis Rhizoma, Ephedra Herba, and Scutellariae Radix had strong PPARγ ligand activity on ELISA. BT powder produced a significant reduction in visceral fat weight in addition to increases in PPARγ mRNA expression and peroxidase activity in visceral fat. BT powder and BT extract considerably decreased fatty acid binding protein-4 (FABP4), although the difference was not statistically significant. Conclusion: Peroxidase catalyzes lipid peroxides. Oxidative stress and inflammation induce FABP4 expression. BT powder was a more effective anti-inflammatory agent than BT extract. Furthermore, FABP4 triggers the ubiquitination and subsequent proteasomal degradation of PPARγ. This suggests that decrease in PPARγ by FABP4 might be restored by treatment with BT powder.

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Fatty acid binding protein-4 (FABP4) is a hypoxia inducible gene that sensitizes mice to liver ischemia/reperfusion injury

Cited by 47 publications

References 41 publications

FABP4 as a key determinant of metastatic potential of ovarian cancer

FABP4 as a key determinant of metastatic potential of ovarian cancer

FABP4 regulates eosinophil recruitment and activation in allergic airway inflammation

Anti‐obesity and anti‐inflammatory effects of peroxisome proliferator activated receptor‐γ induced by bofutsushosan powder versus extract

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