Wnt Signaling and Aging-Related Heart Disorders

Naito, Atsuhiko T.; Shiojima, Ichiro; Komuro, Issei

doi:10.1161/circresaha.110.223776

Cited by 56 publications

(35 citation statements)

References 110 publications

(111 reference statements)

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“…This is in part due to increased competition between canonical Wnt and FOXO signaling for available ␤-catenin (24). Increased FOXO transcriptional activity and decreased Wnt activity have been suggested to play a role in the formation of ␤-amyloid plaques in Alzheimer's disease, as well as agerelated heart disease (55,56). Furthermore, Wnt signaling has been shown to regulate the balance between myogenesis and adipogenesis and regulate insulin sensitivity in myoblasts (36).…”

Section: Discussionmentioning

confidence: 99%

Cross-talk between Insulin and Wnt Signaling in Preadipocytes

Palsgaard

Emanuelli

Winnay

et al. 2012

Journal of Biological Chemistry

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Background: Wnt signaling blocks adipocyte development and is implicated in diabetes and the metabolic syndrome. Results: Wnt stimulates insulin mediators via an insulin/IGF-1 receptor-dependent process; conversely, Wnt co-receptor LRP5 is essential to normal insulin signaling in preadipocytes. Conclusion: Insulin and Wnt signaling pathways interact and are both dependent on LRP5. Significance: Altered Wnt/LRP5 activity can play a role in obesity and insulin resistance.

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Section: Discussionmentioning

confidence: 99%

Cross-talk between Insulin and Wnt Signaling in Preadipocytes

Palsgaard

Emanuelli

Winnay

et al. 2012

Journal of Biological Chemistry

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“…The Wnt/β-catenin signaling pathway is involved in multiple developmental events during embryogenesis and is also implicated in tumorigenesis, cell-fate decisions, proliferation and apoptosis (10,11). Wnt ligands trigger at least three different intracellular signaling cascades: the canonical Wnt pathway, which results in transcriptional regulation of target genes via β-catenin; the planar cell polarity (PCP) pathway; and the Wnt-dependent calcium/protein kinase C (PKC) pathway.…”

Section: Introductionmentioning

confidence: 99%

Caudatin induces cell apoptosis in gastric cancer cells through modulation of Wnt/β-catenin signaling

Zhang

Liu

et al. 2013

Oncology Reports

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Abstract. Caudatin has been reported to trigger apoptosis in several types of cancer cell lines. In the present study, we investigated whether caudatin has therapeutic value in gastric cancer and examined the effects of caudatin on the expression of β-catenin in human gastric carcinoma cell lines. Here, we showed that caudatin treatment resulted in a dose-and time-dependent inhibition of proliferation of the gastric carcinoma cell lines. Cell cycle analysis demonstrated that caudatin induced G0/G1 arrest and downregulated CDK2 levels. In contrast, the expression of the p21 protein was increased. AGS cells treated with caudatin exhibited typical characteristics of apoptosis, which were accompanied by activation of caspase-3, -8, -9 and PARP. Western blot analysis and immunocytochemical staining showed that caudatin induced a reduction in β-catenin expression and this reduction was due to proteosome-mediated degradation. This reduction in β-catenin activation was due to the downregulation of its downstream targets cyclinD1 and c-MYC in all gastric carcinoma cell lines. Furthermore, we demonstrated that gastric adenocarcinoma tissues and AGS cells exhibited abnormal expression of miR-372. Additionally, caudatin downregulated the expression of oncomir miR-372 and miR-21, and upregulated tumor suppressor let-7a miRNA expression. These data revealed that inhibition of Wnt/β-catenin signaling is a novel mechanism of action for caudatin during therapeutic intervention in gastric cancers. IntroductionGastric cancer is one of the most common malignancies and the second leading cause of cancer-related mortality worldwide.Surgery and systemic treatment regimens in combination with radiotherapy and chemotherapy are able to cure this malignancy in the majority of cases. Unfortunately, the young age of typical gastric cancer patients further enhances the time at risk for the side effects of these therapies. Delayed toxicity and the development of secondary malignancies are a serious concern for the current anti-neoplastic armamentarium (1,2). Therefore, it is urgent to further characterize the entity of gastric tumors to better understand and predict their biological behaviors and to identify novel high efficient and low toxic therapeutic agents for the treatment of gastric cancer in clinical practice (3).Modern pharmacologic study proves that C-21 steroidal glycosides are important biological active compounds, which are widely found in the plants of the Asclepiadaceae family and exhibit extensive pharmacological effects such as inhibition of proliferation, induction of apoptosis and inhibition of the invasion of tumor cells (4,5). Caudatin, a C-21 steroidal glycoside, is mainly isolated from the root of Cynanchum bungei Decne in China. Recent studies demonstrated that caudatin induced the apoptosis of HepG2 cells or the SMMC772 cell line (6,7). Wang et al (8) found that caudatin had an inhibitory activity on the secretion of HBsAg and HBV DNA replication. Furthermore, caudatin as a prospective anti-HCC drug with the mechanism...

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“…WLS may control skeletal development through modulation of autocrine and paracrine Wnt signals in a lineage-specific fashion (15). Wnt signalling has also been found to regulate crucial aspects of cardiovascular physiology (differentiation, morphogenesis and progenitor self-renewal), (16) to increase with aging in the heart, (17) and to drive cardiac progenitor cells to differentiate into a fibrogenic lineage, suggesting its involvement in the path-ophysiology of CVD. The MEF2C gene encodes a member of the MADS box transcription enhancer factor 2 (MEF2) family of proteins, which plays a role in myogenesis and is evolutionarily conserved (18).…”

Section: Discussionmentioning

confidence: 99%

Targeted sequencing of genome wide significant loci associated with bone mineral density (BMD) reveals significant novel and rare variants: the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) targeted sequencing study

et al. 2016

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Background Bone mineral density (BMD) is a heritable phenotype that predicts fracture risk. We performed fine-mapping by targeted sequencing at WLS, MEF2C, ARHGAP1/F2 and JAG1 loci prioritized by eQTL and bioinformatic approaches among 56 BMD loci from our previous GWAS meta-analysis. Methods and Results Targeted sequencing was conducted in 1,291 Caucasians from the Framingham Heart Study (n = 925) and Cardiovascular Health Study (n = 366), including 206 women and men with extreme low femoral neck (FN) BMD. A total of 4,964 sequence variants (SNVs) were observed and 80% were rare with MAF <1%. The associations between previously identified SNPs in these loci and BMD, while nominally significant in sequenced participants, were no longer significant after multiple testing corrections. Conditional analyses did not find protein-coding variants that may be responsible for GWAS signals. On the other hand, in the sequenced subjects, we identified novel associations in WLS, ARHGAP1, and 5′ of MEF2C (P-values < 8×10−5; false discovery rate (FDR) q-values < 0.01) that were much more strongly associated with BMD compared to the GWAS SNPs. These associated SNVs are less-common; independent from previous GWAS signals in the same loci; and located in gene regulatory elements. Conclusions Our findings suggest that protein-coding variants in selected GWAS loci did not contribute to GWAS signals. By performing targeted sequencing in GWAS loci, we identified less-common and rare non-coding SNVs associated with BMD independently from GWAS common SNPs, suggesting both common and less-common variants may associate with disease risks and phenotypes in the same loci.

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Wnt Signaling and Aging-Related Heart Disorders

Cited by 56 publications

References 110 publications

Cross-talk between Insulin and Wnt Signaling in Preadipocytes

Cross-talk between Insulin and Wnt Signaling in Preadipocytes

Caudatin induces cell apoptosis in gastric cancer cells through modulation of Wnt/β-catenin signaling

Targeted sequencing of genome wide significant loci associated with bone mineral density (BMD) reveals significant novel and rare variants: the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) targeted sequencing study

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