Enhanced intestinal epithelial cell proliferation in diabetic rats correlates with β-catenin accumulation

Dorfman, Tatiana; Pollak, Yulia; Sohotnik, Rima; Coran, Arnold G.; Bejar, Jacob; Sukhotnik, Igor

doi:10.1530/joe-14-0725

Cited by 12 publications

(9 citation statements)

References 26 publications

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“…34,76,78,84,85 The effect is believed to follow the dissolution of the adherens junctions, the removal of E-cadherin and the consequent release of bound β-catenin into the cytoplasm: E-cadherin exerts a stabilising influence on the levels of β-catenin. 16,[86][87][88] Altered expression or activity of β-catenin has been implicated in regulating proliferation 28,84 and oncogenesis 22,33,75,[89][90][91] being proposed as a 'co-factor' in the initiation of EMT. 92,93 Inhibition of the Wnt/β-catenin pathway inhibits cancer cell proliferation 31,94,95 although others have linked β-catenin activation to reduced growth and increased differentiation.…”

Section: β-Cateninmentioning

confidence: 99%

“…[16][17][18][19][20][21] β-catenin normally exists in association with E-cadherin in junctional complexes so that a fall in E-cadherin expression results in an increase in unbound β-catenin levels in the cytoplasm from where it can enter the nucleus and canas a component of the wingless (Wnt) transduction systemactivate transcription factors that promote increased proliferation and cell migration. [22][23][24][25][26][27][28][29][30][31][32] Any β-catenin which is phosphorylated in the cytoplasm remains trapped there until it is transported to the proteasome for degradation and disposal. 25,33,34 Small molecule inhibitors of β-catenin are able to suppress carcinogenesis.…”

Section: Introductionmentioning

confidence: 99%

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Serine protease modulation of Dependence Receptors and EMT protein expression

McNair

Forrest

Vincenten

et al. 2018

Cancer Biology & Therapy

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Expression of the tumour suppressor Deleted in Colorectal Cancer (DCC) and the related protein neogenin is reduced by the mammalian serine protease chymotrypsin or the bacterial serine protease subtilisin, with increased cell migration. The present work examines whether these actions are associated with changes in the expression of cadherins, β-catenin and vimentin, established markers of the Epithelial-Mesenchymal Transition (EMT) which has been linked with cell migration and tumour metastasis. The results confirm the depletion of DCC and neogenin and show that chymotrypsin and subtilisin also reduce expression of β-catenin in acutely prepared tissue sections but not in human mammary adenocarcinoma MCF-7 or MDA-MB-231 cells cultured in normal media, or primary normal human breast cells. A loss of β-catenin was also seen in low serum media but transfecting cells with a dcc-containing plasmid induced resistance. E-cadherin was not consistently affected but vimentin was induced by low serum-containing media and was increased by serine proteases in MCF-7 and MDA-MB-231 cells in parallel with increased wound closure. Vimentin might contribute to the promotion of cell migration. The results suggest that changes in EMT proteins depend on the cells or tissues concerned and do not parallel the expression of DCC and neogenin. The increased cell migration induced by serine proteases is not consistently associated with the expression of the EMT proteins implying either that the increased migration may be independent of EMT or supporting the view that EMT is not itself consistently related to migration. (241).

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Section: β-Cateninmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Serine protease modulation of Dependence Receptors and EMT protein expression

McNair

Forrest

Vincenten

et al. 2018

Cancer Biology & Therapy

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“…Diabetes‐induced hyperglycemia has been reported to bring about oxidative stress and apoptosis in the kidney (Wagener et al., 2009). Caspase‐3 protein levels have been reported to decrease in different tissues of diabetic rats (Dorfman et al., 2015; Hamza, Fikry, Abdallah, & Amin, 2018; Yuan et al., 2016). Bcl‐2 protein expression has been reported to increase in diabetic rats (He, Sun, & Huang, 2018).…”

Section: Discussionmentioning

confidence: 99%

Protective effect of pristine C60 fullerene nanoparticle in combination with curcumin against hyperglycemia‐induced kidney damage in diabetes caused by streptozotocin

Demir

Aslan

2020

J. Food Biochem.

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Today, diabetes has become a significant metabolic disease.Sedentary lifestyle and obesity increase the incidence of this disease. The International Diabetes Federation states that approximately 425 million people are affected from diabetes worldwide as of now, but by 2045, the number of patients is projected to exceed 600 million (Matoba et al., 2020).Diabetes develops due to deficiency of insulin secretion or decreased tissue sensitivity to insulin. It leads to complications such as uncontrolled hyperglycemia, diabetic nephropathy, cardiomyopathy, retinopathy in diabetic patients. Diabetic nephropathy is a common complication linked to type-1 and type-2 diabetes, with end-term kidney failure seen in almost 30% of individuals with diabetes (Chowdhury, Ghosh, Das, & Sil, 2019). There are numerous studies reporting that chronic hyperglycemia causes an increase in

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“…In general, the signaling most closely connected to the abnormal proliferation and differentiation of IESCs is Wnt signaling [2]. Enhanced intestinal epithelial cell proliferation in diabetes mellitus (DM) has been demonstrated not only in experimental diabetic mice but also in recent clinical trials [4, 5]. Excessive activation of Wnt signaling in stem cells increases intestinal epithelial cell proliferation and even promotes formation of adenomas [6].…”

Section: Introductionmentioning

confidence: 99%

Sox9 transcriptionally regulates Wnt signaling in intestinal epithelial stem cells in hypomethylated crypts in the diabetic state

Huang

et al. 2017

Stem Cell Res Ther

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BackgroundDistinctive structures called crypts harbor intestinal epithelial stem cells (IESCs) which generate progenitor and terminally differentiated cells in the intestinal epithelium. Mammalian IESCs and their daughter cells require the participation of DNA methylation and the transcription factor Sox9 for proliferation and differentiation. However, the association between Sox9 and DNA methylation in this process remains elusive.MethodsThe DNA methylation of small intestinal epithelial crypts in db/db mice was detected via combining methylated DNA immunoprecipitation with microarray hybridization. DNA methylation of Sox9 promoter in crypts and IESCs was validated using bisulfite sequence analysis. The target sequence of the transcription factor Sox9 in IESCs was investigated via chromatin immunoprecipitation (ChIP) combined with deep sequencing (ChIP-seq).ResultsIncreased Sox9 expression is accompanied by the loss of methylation in its promoter in IESCs. Sox9 targets the enhancers of the Wnt signaling pathway-related genes. Sox9 predominantly acts as a transcriptional activator at proximal enhancers of Wnt4, Tab2, Sox4, and Fzd8, but also functions as a potential transcriptional inhibitor at a distant enhancer of Cdk1. Lack of Sox9 transcriptional activation in specific repressors of the Wnt signaling pathway leads to the loss of intrinsic inhibitory action and ultimately produces overactivation of this pathway in db/db mice.ConclusionsOur study sheds light on the connections among DNA methylation, transcription factor modulation, and Wnt signaling in IESCs in the diabetic state. Hypomethylation in the Sox9 promoter is correlated to increased Sox9 expression in db/db IESCs. Although there is increased expression of Sox9 in db/db IESCs, the loss of Sox9 transcriptional activation in specific repressors of the Wnt signaling pathway might result in abnormalities in this pathway.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0507-4) contains supplementary material, which is available to authorized users.

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Enhanced intestinal epithelial cell proliferation in diabetic rats correlates with β-catenin accumulation

Cited by 12 publications

References 26 publications

Serine protease modulation of Dependence Receptors and EMT protein expression

Serine protease modulation of Dependence Receptors and EMT protein expression

Protective effect of pristine C60 fullerene nanoparticle in combination with curcumin against hyperglycemia‐induced kidney damage in diabetes caused by streptozotocin

Sox9 transcriptionally regulates Wnt signaling in intestinal epithelial stem cells in hypomethylated crypts in the diabetic state

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