Background: As Wnt/β-catenin/glycogen synthase kinase 3β (GSK3β) signaling has been implicated in myocardial injury and diabetic cardiomyopathy (DCM) is a major part of diabetic cardiovascular complications, we therefore investigated the alterations of Wnt/β-catenin/GSK3β signaling during the development of DCM.
Methods: The rat model of diabetes mellitus (DM) was established using a single intraperitoneal injection of streptozotocin (STZ, 60 mg/kg). The alterations of Wnt/β-catenin/GSK3β signaling were determined 4, 8, and 12 weeks following DM using Western blotting, immunohistochemistry, and quantitative real-time reverse transcriptase polymerase chain reaction. Cardiac pathology changes were evaluated using hematoxylin and eosin, Masson trichromatic, and terminal dUTP nick-end labeling staining.
Results: Histological analyses revealed that DM induced significant myocardial injury and progressive cardiomyocyte apoptosis. The protein and mRNA levels of Wnt2, β-catenin, and c-Myc were progressively increased 4, 8, and 12 weeks following DM. The expression of T-cell factor 4 and phosphorylated of GSK3β on Ser9 were progressively increased. However, the expression of the endogenous Wnt inhibitor Dickkopf-1 was increased after STZ injection and then decreased as DCM developed.
Conclusion: Wnt/β-catenin/GSK3β signaling pathway is activated in the development of DCM. Further investigation into the role of Wnt signaling during DCM will functionally find novel therapeutic target for DCM.
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http://dx.doi.org/10.1016/j.carpath.2014.12.002 | DOI Listing |
First-line immune checkpoint inhibitor (ICI) combinations show responses in subsets of hepatocellular carcinoma (HCC) patients. Nearly half of HCCs are Wnt-active with mutations in (encoding for β-catenin), , or , and demonstrate limited benefit to ICI due to an immune excluded tumor microenvironment. We show significant tumor responses in multiple β-catenin-mutated immunocompetent HCC models to a novel siRNA encapsulated in lipid nanoparticle targeting (LNP-CTNNB1).
View Article and Find Full Text PDFJ Oral Biosci
December 2024
Division of Anatomical and Cellular Pathology, Department of Pathology, Iwate Medical University, 1-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan. Electronic address:
Objective: This study aimed to evaluate the role of the chromodomain helicase DNA-binding protein 3 (CHD3) in tooth morphogenesis in Chd3 knockout mice.
Methods: Chd3 knockout mice were generated using the CRISPR-Cas9 method. Mandibular first molars were extracted from the mice and their littermates and morphometrically analyzed.
Background: Diabetes mellitus (DM) is a prevalent chronic disease that is becoming increasingly common worldwide and can lead to a number of dangerous complications. The Wnt signaling pathway is important for the onset and progression of diabetes. Wnt3a is a typical Wnt ligand that can increase the stability of β-catenin, control TCF7L2 expression, promote β-cell proliferation, and reduce apoptosis.
View Article and Find Full Text PDFInt Immunopharmacol
December 2024
Department of Nephrology, the Second Affiliated Hospital of Harbin Medical University, Harbin, China. Electronic address:
Background: Adipose mesenchymal stem cells (ADSCs) exert beneficial effects on kidney disease through a paracrine mechanism. However, the specific molecular mechanisms by which ADSCs treat renal fibrosis are not yet fully understood. Therefore, it is crucial to clarify the therapeutic effects of ADSC-derived extracellular vesicles (ADSC-EVs) on the progression of renal fibrosis and their underlying mechanisms.
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