Vitamin D Receptor Activation in Liver Macrophages Protects Against Hepatic Endoplasmic Reticulum Stress in Mice

Zhou, Ying; Dong, Bingning; Kim, Kang Ho; Choi, Sung-Woo; Sun, Zhen; Wu, Nan; Wu, Yifan; Scott, Jessica; Moore, David D.

doi:10.1002/hep.30887

Cited by 45 publications

(38 citation statements)

References 44 publications

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“…Multiple previous literatures have confirmed that the activation state of VDR can modulate the functions of non-parenchymal and parenchymal liver cells, such as fibrogenesis, integrity of biliary epithelial cells, liver cancer, and BA metabolism. Recently, two studies published in Hepatology further emphasized the importance of VDR in regulating inflammatory response, and VDR activation by VDR ligands may be useful as a potential method for treating multiple liver diseases (Dong et al, 2019;Zhou et al, 2019). In previous studies, vitamin D3 has been proved to abate fibrosis and modulate BA regulatory genes in BDL-induced cholestasis (Ogura et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Calcipotriol Inhibits NLRP3 Signal Through YAP1 Activation to Alleviate Cholestatic Liver Injury and Fibrosis

Wang

et al. 2020

Front. Pharmacol.

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Cholestasis is common in multiple clinical circumstances. The NOD-like receptor protein 3 (NLRP3) inflammasome pathway has been demonstrated to play an important role in liver injury and fibrosis induced by cholestasis. We previously proved that MCC950, a selective NLRP3 inhibitor, alleviates liver fibrosis and injury in experimental liver cholestasis induced by bile-duct ligation (BDL) in mice. Herein, we investigate the role of calcipotriol, a potent vitamin D receptor agonist, in experimental liver cholestasis, test its therapeutic efficacy, and explore its potential protective mechanism. C57BL/6 mice were made to undergo BDL or fed the 0.1% 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet to establish two classic cholestatic models. Calcipotriol was administered intraperitoneally to these mice daily. Serum makers of liver damage and integrity, liver histological changes, levels of liver pro-fibrotic markers, bile acid synthetases and transporters were measured in vivo. The underlying mechanism by which calcipotriol alleviates cholestatic liver injury and fibrosis was further investigated. The results of the current study demonstrated that calcipotriol supplement significantly alleviate cholestatic liver injury and fibrosis. Moreover, calcipotriol supplement markedly inhibited NLRP3 inflammasome pathway activation to alleviate liver injury and fibrosis in vivo and inhibit hepatic stellate cell (HSC) activation in vitro. In addition, VDR agonist calcipotriol exert inhibitory effect on NLRP3 inflammasome activation through activating yes-associated protein 1 (YAP1). In conclusion, our findings proved that calcipotriol suppressed the NLRP3 signal by activating YAP1 to alleviate liver injury and retard fibrogenesis in cholestasis.

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Section: Discussionmentioning

confidence: 99%

Calcipotriol Inhibits NLRP3 Signal Through YAP1 Activation to Alleviate Cholestatic Liver Injury and Fibrosis

Wang

et al. 2020

Front. Pharmacol.

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“…IL-1β, CRP, TNF-α, and IL-6 are commonly used indicators to assess the risk of cardiovascular events ( 41 , 42 ). These pro-inflammatory cytokines are also closely related to the occurrence and prognosis of NAFLD disease ( 43 , 44 ). Therefore, regulating lipids and inhibiting inflammation have become an important way to combat AS in recent years.…”

Section: Discussionmentioning

confidence: 99%

CML/RAGE Signal Bridges a Common Pathogenesis Between Atherosclerosis and Non-alcoholic Fatty Liver

et al. 2020

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Non-alcoholic fatty liver disease (NAFLD) has become a common chronic disease in the world. NAFLD is not only a simple intrahepatic lesion, but also affects the occurrence of a variety of extrahepatic complications. In particular, cardiovascular complications are particularly serious, which is the main cause of death in patients with NAFLD. To study the relationship between NAFLD and AS may be a new way to improve the quality of life in patients with NAFLD. As we all known, inflammatory response plays an important role in the occurrence and development of NAFLD and AS. In this study, we found that the accumulation of Nε-carboxymethyllysine (CML) in the liver leads to hepatic steatosis. CML can induce the expression of interleukin (IL-1β), interleukin (IL-6), tumor necrosis factor (TNF-α), C-reactionprotein (CRP) by binding with advanced glycosylation end-product receptor (RAGE) and accelerate the development of AS. After silencing RAGE expression, the expression of pro-inflammatory cytokines was inhibited and liver and aorta pathological changes were relieved. In conclusion, CML/RAGE signal promotes the progression of non-alcoholic fatty liver disease and atherosclerosis. We hope to provide new ideas for the study of liver vascular dialogue in multi organ communication.

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“…Retrospective data and indirect evidence also show a possible role for vitamin D in reducing complications attributed to and the cytokine storm itself[ 52 ]. Moreover, recent research revealed that vitamin D receptor signaling in macrophages regulates a shift between proinflammatory and anti-inflammatory activation during ER stress-induced inflammation[ 53 ]. Thus, supplementation within recommended upper safety limits, for specific nutrients such as vitamins C and D, warrants optimal nutritional status to insure a well-functioning immune system protecting against viral infections[ 54 ].…”

Section: Discussionmentioning

confidence: 99%

Association between population vitamin D status and SARS-CoV-2 related serious-critical illness and deaths: An ecological integrative approach

Papadimitriou¹,

Vassaras²,

Holick³

2021

WJV

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BACKGROUND Vitamin D population status may have possible unappreciated consequences to the coronavirus disease 2019 (COVID-19) pandemic. Α significant association between vitamin D sufficiency and reduction in clinical severity and inpatient mortality from COVID-19 disease has recently been shown, while a recent study has claimed lower COVID-19 cases in European countries with a better vitamin D status. Low serum 25-hydroxyvitamin-D [25(OH)D] was identified as an independent risk factor for COVID-19 infection and hospitalization, and administration of 0.532 mg (21280 IU) of calcifediol or 25(OH)D, followed by 0.266 mg on days 3 and 7 and then weekly until discharge or intensive care unit admission significantly reduced the need for intensive care unit treatment. AIM To elucidate the role of vitamin D European population status in the COVID-19 pandemic, data from the Worldometer were analyzed. METHODS Linear regression explored the correlation between published representative-standardized population vitamin D concentrations and the number of total cases/million (M), recovered/M, deaths/M and serious-critically ill/M from COVID-19 for 26 European countries populated > 4 M (Worldometer). Life expectancy was analyzed with semi-parametric regression. Weighted analysis of variance/analysis of covariance evaluated serious-critical/M and deaths/M by the vitamin D population status: Deficient < 50, insufficient: 50-62.5, mildly insufficient > 62.5-75 and s ufficient > 75 nmol/L, while controlling for life expectancy for deaths/M. Statistical analyses were performed in XLSTAT LIFE SCIENCE and R (SemiPar Library). RESULTS Linear regression found no correlation between population vitamin D concentrations and the total cases-recovered/M, but negative correlations predicting a reduction of 47%-64%-80% in serious-critical illnesses/M and of 61%-82%-102.4% in deaths/M further enhanced when adapting for life expectancy by 133-177-221% if 25(OH)D concentrations reach 100-125-150 nmol/L, sustained on August 15, 2020, indicating a truthful association. Weighted analysis of variance was performed to evaluate serious-critical/M ( r 2 = 0.22) by the vitamin D population status and analysis of covariance the deaths/M ( r 2 = 0.629) controlling for life expectancy ( r 2 = 0.47). Serious-critical showed a decreasing trend ( P < 0.001) from population status deficient ( P < 0.001) to insufficient by 9.2% ( P < 0.001), to mildly insufficient by 47.6% ( P < 0.044) and to sufficient by 100% (reference, P < 0.001). For deaths/M the respective decreasing trend ( P < 0.001) was 62.9% from deficient ( P < 0....

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Vitamin D Receptor Activation in Liver Macrophages Protects Against Hepatic Endoplasmic Reticulum Stress in Mice

Cited by 45 publications

References 44 publications

Calcipotriol Inhibits NLRP3 Signal Through YAP1 Activation to Alleviate Cholestatic Liver Injury and Fibrosis

Calcipotriol Inhibits NLRP3 Signal Through YAP1 Activation to Alleviate Cholestatic Liver Injury and Fibrosis

CML/RAGE Signal Bridges a Common Pathogenesis Between Atherosclerosis and Non-alcoholic Fatty Liver

Association between population vitamin D status and SARS-CoV-2 related serious-critical illness and deaths: An ecological integrative approach

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