Macrophage-derived thrombospondin 1 promotes obesity-associated non-alcoholic fatty liver disease

Gwag, Taesik; Mooli, Raja Gopal Reddy; Li, Dong; Lee, Sangderk; Lee, Eun Young; Wang, Shuxia

doi:10.1016/j.jhepr.2020.100193

Cited by 32 publications

(38 citation statements)

References 48 publications

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“…Consistently, a previous study showed that SMPDL3B modulates insulin receptor signaling and thereby contributes to the production of ceramide-1-phosphate ( Fornoni et al, 2014 ; Mallela et al, 2019 ; Mitrofanova et al, 2019 ). Moreover, macrophage-derived thrombospondin 1 promotes obesity-associated non-alcoholic fatty liver disease through suppressing the expression of SMPDL3B ( Gwag et al, 2021 ). Together, these results indicated that SMPDL3B may regulate starch and sucrose metabolism via modulating insulin signaling in AML cells.…”

Section: Discussionmentioning

confidence: 99%

SMPDL3B Predicts Poor Prognosis and Contributes to Development of Acute Myeloid Leukemia

Zhu

2021

Front. Mol. Biosci.

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Background: Acute myeloid leukemia (AML), characterized by the low cure rate and high relapse, urgently needs novel diagnostic or prognostic biomarkers and potential therapeutic targets. Sphingomyelin Phosphodiesterase Acid Like 3B (SMPDL3B) is a negative regulator of Toll-like receptor signaling that plays important roles in the interface of membrane biology and innate immunity. However, the potential role of SMPDL3B in human cancer, especially in AML, is still unknown.Methods: The expression of SMPDL3B in AML samples was investigated through data collected from Gene Expression Omnibus (GEO). Association between SMPDL3B expression and clinicopathologic characteristics was analyzed with the chi-square test. Survival curves were calculated by the Kaplan–Meier method. Cox univariate and multivariate analyses were used to detect risk factors for overall survival. The biological functions of SMPDL3B in human AML were investigated both in vitro and in vivo.Results: Expression of SMPDL3B mRNA was significantly upregulated in human AML samples and closely correlated to cytogenetics risk and karyotypes. Elevated expression of SMPDL3B was associated with poor overall survival and emerged as an independent predictor for poor overall survival in human AML. Blocked SMPDL3B expression inhibited AML cells growth both in vitro and in vivo via promoting cell apoptosis.Conclusion: Taken together, our results demonstrate that SMPDL3B could be used as an efficient prognostic biomarker and represent a potential therapeutic target for human AML.

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Section: Discussionmentioning

confidence: 99%

SMPDL3B Predicts Poor Prognosis and Contributes to Development of Acute Myeloid Leukemia

Zhu

2021

Front. Mol. Biosci.

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“…TSP-1 deletion in adipocytes does not protect mice from diet-induced NAFLD/NASH, whereas myeloid/macrophagespecific TSP-1 deletion protects mice against liver injury. Autocrine-acting macrophagederived TSP-1 suppresses SMPDL3B expression, thereby increasing TLR4-mediated proinflammatory signaling and promoting NAFLD progression [121]. Recently, BMP-1 was shown to be an activator of TSP-1 and an agonist of TGF-β signaling [122].…”

Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 99%

“…Autocrine-acting macrophage-derived TSP-1 suppresses SMPDL3B expression, thereby increasing Toll-like receptor 4-mediated proinflammatory signalling and promoting NAFLD progression. 121 Recently, BMP-1 was shown to be an activator of TSP-1 and an agonist of TGF-β signalling. 122 Besides acting as a vital regulator of TGF-β activation, TSP also has TGF-β independent biological functions, e.g.…”

Section: Activation Of Tgf-β Signalling Ligands From Ecm Storagementioning

confidence: 99%

Transforming growth factor β latency: A mechanism of cytokine storage and signalling regulation in liver homeostasis and disease

Fan

Link

et al. 2022

JHEP Reports

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Summary Transforming growth factor-β (TGF-β) is a potent effector in the liver, which is involved in a plethora of processes initiated upon liver injury. TGF-β affects parenchymal, non-parenchymal, and inflammatory cells in a highly context-dependent manner. Its bioavailability is critical for a fast response to various insults. In the liver – and probably in other organs – this is made possible by the deposition of a large portion of TGF-β in the extracellular matrix as an inactivated precursor form termed latent TGF-β (L-TGF-β). Several matrisomal proteins participate in matrix deposition, latent complex stabilisation, and activation of L-TGF-β. Extracellular matrix protein 1 (ECM1) was recently identified as a critical factor in maintaining the latency of deposited L-TGF-β in the healthy liver. Indeed, its depletion causes spontaneous TGF-β signalling activation with deleterious effects on liver architecture and function. This review article presents the current knowledge on intracellular L-TGF-β complex formation, secretion, matrix deposition, and activation and describes the proteins and processes involved. Further, we emphasise the therapeutic potential of toning down L-TGF-β activation in liver fibrosis and liver cancer.

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“…Blocking macrophage scavenger receptor 1 (MSR1) in vitro reduced saturated fatty acid-induced inflammatory gene expression in primary MFs and in vivo administration of an anti-MSR1 antibody ameliorated liver inflammation in a NAFLD mouse model [ 155 , 180 ]. Thrombospondin-1 (TSP1) can induce pro-inflammatory gene expression in MFs and MF-specific TSP1 −/− mice showed reduced liver injury in experimental NAFLD, suggesting MF-specific TSP1-modulation as a therapeutic strategy [ 196 ]. Various other targets have been proposed in NAFLD, of which their in vivo ameliorating effects are reported to be mediated by modulating inflammatory gene expression in MFs, including glucocorticoid-induced leucine zipper [ 197 ], hypoxia-inducible factor 1α [ 198 , 199 , 200 ], vitamin D receptor [ 201 ], farnesoid X receptor [ 202 ] and peroxisome proliferator-activated receptors (PPARs) [ 185 ].…”

Section: Macrophages During Gut-liver Axis Disruption In Chronic Liver Diseasementioning

confidence: 99%

The Gut–Liver Axis in Chronic Liver Disease: A Macrophage Perspective

Muynck

Vanderborght

Vlierberghe

et al. 2021

Cells

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Chronic liver disease (CLD) is a growing health concern which accounts for two million deaths per year. Obesity, alcohol overconsumption, and progressive cholestasis are commonly characterized by persistent low-grade inflammation and advancing fibrosis, which form the basis for development of end-stage liver disease complications, including hepatocellular carcinoma. CLD pathophysiology extends to the intestinal tract and is characterized by intestinal dysbiosis, bile acid dysregulation, and gut barrier disruption. In addition, macrophages are key players in CLD progression and intestinal barrier breakdown. Emerging studies are unveiling macrophage heterogeneity and driving factors of their plasticity in health and disease. To date, in-depth investigation of how gut–liver axis disruption impacts the hepatic and intestinal macrophage pool in CLD pathogenesis is scarce. In this review, we give an overview of the role of intestinal and hepatic macrophages in homeostasis and gut–liver axis disruption in progressive stages of CLD.

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Macrophage-derived thrombospondin 1 promotes obesity-associated non-alcoholic fatty liver disease

Cited by 32 publications

References 48 publications

SMPDL3B Predicts Poor Prognosis and Contributes to Development of Acute Myeloid Leukemia

SMPDL3B Predicts Poor Prognosis and Contributes to Development of Acute Myeloid Leukemia

Transforming growth factor β latency: A mechanism of cytokine storage and signalling regulation in liver homeostasis and disease

The Gut–Liver Axis in Chronic Liver Disease: A Macrophage Perspective

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