The upside-downside nature of Vitamin D signaling in liver

Scott, Melanie J.

doi:10.1002/jlb.3ce0519-157r

Cited by 1 publication

(4 citation statements)

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“…A complex of proteins and repressors can also regulate VDR activity in repressing gene transcription [53]. The nongenomic pathway refers to the binding of 1,25(OH) 2 D 3 to the VDR membrane, which activates GPCR-mediated calcium (Ca 2+ ) channels and initiates Ca 2+ influx into the cell [54]. Calcium ions act as messengers that mediate intracellular processes of signal transduction [55].…”

Section: Vitamin D-vdr Signaling In Cellsmentioning

confidence: 99%

“…Calcium ions act as messengers that mediate intracellular processes of signal transduction [55]. Ca 2+ activity can induce downstream signaling pathways, including activation of the AKT pathway and mTORC1 signaling, as well as autophagy, which can exert inflammatory and anti-inflammatory effects [54]. Activation of the PKC and ERK/MAPK signaling pathways is also mediated by the binding of vitamin D to the membrane VDR, which may lead to the production of pro-or anti-inflammatory mediators, depending on additional stimuli [54] (Figure 2).…”

Section: Vitamin D-vdr Signaling In Cellsmentioning

confidence: 99%

“…Ca 2+ activity can induce downstream signaling pathways, including activation of the AKT pathway and mTORC1 signaling, as well as autophagy, which can exert inflammatory and anti-inflammatory effects [54]. Activation of the PKC and ERK/MAPK signaling pathways is also mediated by the binding of vitamin D to the membrane VDR, which may lead to the production of pro-or anti-inflammatory mediators, depending on additional stimuli [54] (Figure 2). Bikle [53] proposed a more detailed description of the nongenomic effects of vitamin D. Binding of vitamin D to the membrane activates the VDR-G protein.…”

Section: Vitamin D-vdr Signaling In Cellsmentioning

confidence: 99%

“…pro-or anti-inflammatory mediators, depending on additional stimuli [54] (Figure 2). Bikle [53] proposed a more detailed description of the nongenomic effects of vitamin D. Binding of vitamin D to the membrane activates the VDR-G protein.…”

Section: Vitamin D-vdr Signaling In Cellsmentioning

confidence: 99%

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Gene Polymorphisms and Biological Effects of Vitamin D Receptor on Nonalcoholic Fatty Liver Disease Development and Progression

Tourkochristou

Mouzaki

Triantos

2023

IJMS

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Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, with increasing prevalence worldwide. The genetic and molecular background of NAFLD pathogenesis is not yet clear. The vitamin D/vitamin D receptor (VDR) axis is significantly associated with the development and progression of NAFLD. Gene polymorphisms may influence the regulation of the VDR gene, although their biological significance remains to be elucidated. VDR gene polymorphisms are associated with the presence and severity of NAFLD, as they may influence the regulation of adipose tissue activity, fibrosis, and hepatocellular carcinoma (HCC) development. Vitamin D binds to the hepatic VDR to exert its biological functions, either by activating VDR transcriptional activity to regulate gene expression associated with inflammation and fibrosis or by inducing intracellular signal transduction through VDR-mediated activation of Ca2+ channels. VDR activity has protective and detrimental effects on hepatic steatosis, a characteristic feature of NAFLD. Vitamin D-VDR signaling may control the progression of NAFLD by regulating immune responses, lipotoxicity, and fibrogenesis. Elucidation of the genetic and molecular background of VDR in the pathophysiology of NAFLD will provide new therapeutic targets for this disease through the development of VDR agonists, which already showed promising results in vivo.

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Section: Vitamin D-vdr Signaling In Cellsmentioning

confidence: 99%