The potential role of regucalcin in kidney cell regulation: Involvement in renal failure (Review)

Yamaguchi, Masayoshi

doi:10.3892/ijmm.2015.2343

Cited by 11 publications

(9 citation statements)

References 73 publications

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“…Studies on in vivo RGN KO mice also revealed that RGN is related to the pathogenesis of diabetic nephropathy, nonalcoholic fatty liver disease, and hepatic steatosis [10,11]. We also found support for a physiological role of RGN in maintaining the function of kidney proximal tubular epithelial cells [12]. Diabetic nephropathy rats were shown to exhibit downregulated expression of RGN expression in kidney tissue and decreased amounts of RGN-present exosomes in urine [13].…”

supporting

confidence: 63%

Regucalcin enhances adipocyte differentiation and attenuates inflammation in 3T3‐L1 cells

et al. 2020

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Dysregulation of adipocyte differentiation and dysfunction play key roles in the pathogenesis of obesity and associated disorders such as diabetes and metabolic syndrome, and as such, a better understanding of the molecular mechanism of adipogenesis may help to elucidate the pathological condition of obesity and its associated disorders. Regucalcin (RGN) plays multiple regulatory roles in intracellular Ca 2+ signaling pathways in mammalian cells. Here, we report that overexpression of RGN enhances lipid accumulation in 3T3‐L1 adipocyte cells after adipogenic stimulation, accompanied by upregulation of adipocyte differentiation marker proteins. In contrast, genetic disruption of RGN inhibited adipogenic stimulation‐induced differentiation of 3T3‐L1 cells. Furthermore, RGN overexpression in differentiated 3T3‐L1 adipocytes blocked inflammatory crosstalk between 3T3‐L1 adipocytes and RAW264.7 macrophages in a transwell coculture system. Knockdown of RGN expression in cocultured 3T3‐L1 adipocytes enhanced their susceptibility to RAW264.7 macrophage‐mediated inflammation. These results suggest that RGN is required for 3T3‐L1 adipocyte differentiation and that it exerts anti‐inflammatory activity against 3T3‐L1 adipocyte inflammation after coculture with RAW264.7 macrophages. Thus, RGN may be a novel regulator of adipocyte differentiation and act as a suppressor of inflammation in macrophage‐infiltrated adipocyte tissue.

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confidence: 63%

Regucalcin enhances adipocyte differentiation and attenuates inflammation in 3T3‐L1 cells

et al. 2020

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“…Our data suggest that regucalcin overexpression causes G1 and G2/M phase cell cycle arrest in A498 cells. supporting the view that regucalcin plays a role in cell cycle arrest (22)(23)(24)(25)(26), and we demonstrate herein that thus is also the case in A498 cells.…”

Section: Discussionsupporting

confidence: 91%

“…The gene for regucalcin, which was discovered as a calcium-binding protein (15,16), is localized on the X chromosome (17)(18)(19). Regucalcin is expressed in various types of cells and tissues (20,21), and has been demonstrated to play multifunctional roles in the regulation of manifold cells (21)(22)(23)(24). Regucalcin has been shown to maintain calcium homeostasis, inhibit various signaling pathways involving various protein kinases and protein phosphatases, suppress cytosolic protein synthesis and nuclear DNA and RNA synthesis, and regulate nuclear gene expression in cells (22)(23)(24)(25).…”

Section: Introductionmentioning

confidence: 99%

“…Regucalcin is expressed in various types of cells and tissues (20,21), and has been demonstrated to play multifunctional roles in the regulation of manifold cells (21)(22)(23)(24). Regucalcin has been shown to maintain calcium homeostasis, inhibit various signaling pathways involving various protein kinases and protein phosphatases, suppress cytosolic protein synthesis and nuclear DNA and RNA synthesis, and regulate nuclear gene expression in cells (22)(23)(24)(25). Moreover, regucalcin has been shown to suppress proliferation (26) and apoptosis (27) mediated through various signaling factors in various types of cells.…”

Section: Introductionmentioning

confidence: 99%

“…In the present study, furthermore, we investigated whether regucalcin plays a role as a suppressor in human RCC. Regucalcin is expressed in rat kidney proximal tubular epithelial cells (20,21) and plays a physiological and pathophysiological role in cell regulation and metabolic disorder in the kidney (24). Of note, the gene expression and protein levels of regucalcin are downregulated in the kidney tumor tissues of human subjects (29,30).…”

Section: Introductionmentioning

confidence: 99%

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Prolonged survival of renal cancer patients is concomitant with a higher regucalcin gene expression in tumor tissues: Overexpression of regucalcin suppresses the growth of human renal cell carcinoma cells in vitro

et al. 2018

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Renal cell carcinoma (RCC), which is a type of cancer found in the kidney tubule, is among the 10 most frequently occurring human cancers. Regucalcin plays a potential role as a regulator of transcriptional activity, and its downregulated expression or activity may contribute to the promotion of human cancers. In this study, we investigated the involvement of regucalcin in human RCC. Regucalcin expression was compared in 23 normal and 29 tumor samples of kidney cortex tissues of patients with clear cell RCC obtained through the Gene Expression Omnibus (GEO) database (GSE36895). Regucalcin expression was downregulated in the tumor tissues. The prolonged survival of patients with clear cell RCC was demonstrated to be associated with a higher regucalcin gene expression in the TCGA dataset. The overexpression of regucalcin suppressed the colony formation, proliferation and the death of human clear cell RCC A498 cells in vitro. Mechanistically, the overexpression of regucalcin induced the G1 and G2/M phase cell cycle arrest of A498 cells through the suppression of multiple signaling components, including Ras, PI3 kinase, Akt and mitogen-activated protein (MAP) kinase. Importantly, the overexpression of regucalcin led to an elevation in the levels of the tumor suppressors, p53, Rb and the cell cycle inhibitor, p21. The levels of the transcription factors, c-fos, c-jun, nuclear factor-κB p65, β-catenin and signal transducer and activator of transcription 3, were suppressed by regucalcin overexpression. On the whole, the findings of this study suggest that regucalcin plays a suppressive role in the promotion of human RCC. The overexpression of regucalcin by gene delivery systems may thus prove to be a novel therapeutic strategy for RCC.

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Implementation of Proteomics Biomarkers in Nephrology: From Animal Models to Human Application?

Klein

Schanstra

2018

Proteomics Clinical Apps

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Preclinical animal models are extensively used in nephrology. In this review, the utility of performing proteome analysis of kidney tissue or urine in such models and transfer of the results to human application has been assessed. Analysis of the literature identified 68 relevant publications. Pathway analysis of the reported proteins clearly indicated links with known biological processes in kidney disease providing validation of the observed changes in the preclinical models. However, although most studies focused on the identification of early markers of kidney disease or prediction of its progression, none of the identified makers has made it to substantial validation in the clinic or at least in human samples. Especially in renal disease where urine is an abundant source of biomarkers of diseases of the kidney and the urinary tract, it therefore appears that the focus should be on human material based discovery studies. In contrast, the most valid information of proteome analysis of preclinical models in nephrology for translation in human disease resides in studies focusing on drug evaluation, both efficacy for translation to the clinic and for mechanistic insight.

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The potential role of regucalcin in kidney cell regulation: Involvement in renal failure (Review)

Cited by 11 publications

References 73 publications

Regucalcin enhances adipocyte differentiation and attenuates inflammation in 3T3‐L1 cells

Regucalcin enhances adipocyte differentiation and attenuates inflammation in 3T3‐L1 cells

Prolonged survival of renal cancer patients is concomitant with a higher regucalcin gene expression in tumor tissues: Overexpression of regucalcin suppresses the growth of human renal cell carcinoma cells in vitro

Implementation of Proteomics Biomarkers in Nephrology: From Animal Models to Human Application?

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