Β-catenin In Rats Research Articles

Accumulated β-catenin is associated with human atrial fibrosis and atrial fibrillation

BackgroundAtrial fibrillation (AF) is associated with increased risk of stroke and mortality. It has been reported that the process of atrial fibrosis was regulated by β-catenin in rats with AF. However, pathophysiological mechanisms of this process in human with AF remain unclear. This study aims to investigate the possible mechanisms of β-catenin in participating in the atrial fibrosis using human right atrial appendage (hRAA) tissues .MethodsWe compared the difference of β-catenin expression in hRAA tissues between the patients with AF and sinus rhythm (SR). The possible function of β-catenin in the development of AF was also explored in mice and primary cells.ResultsFirstly, the space between the membrane of the gap junctions of cardiomyocytes was wider in the AF group. Secondly, the expression of the gap junction function related proteins, Connexin40 and Connexin43, was decreased, while the expression of β-catenin and its binding partner E-cadherin was increased in hRAA and cardiomyocytes of the AF group. Thirdly, β-catenin colocalized with E-cadherin on the plasma membrane of cardiomyocytes in the SR group, while they were dissociated and accumulated intracellularly in the AF group. Furthermore, the expression of glycogen synthase kinase 3β (GSK-3β) and Adenomatous Polyposis Coli (APC), which participated in the degradation of β-catenin, was decreased in hRAA tissues and cardiomyocytes of the AF group. Finally, the development of atrial fibrosis and AF were proved to be prevented after inhibiting β-catenin expression in the AF model mice.ConclusionsBased on human atrial pathological and molecular analyses, our findings provided evidence that β-catenin was associated with atrial fibrosis and AF progression.

COX-2/PGE2 facilitates fracture healing by activating the Wnt/β-catenin signaling pathway.

The aim of this study was to explore the influence of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) on fracture healing by activating the Wnt/β-catenin signaling pathway. In this study, 36 adult Sprague-Dawley (SD) rats raised in our laboratory were selected as research objects. The rats were subjected to fracture surgery on the middle part of the right femoral shaft. Subsequently, they were randomly divided into the control group and experimental groups (including experimental group A and experimental group B). Rats in experimental group A were injected with PGE 2 or COX-2 selective inhibitor NS-398, while rats in experimental group B were injected with PGE2 (5 μmol/L). Meanwhile, rats in the control group were injected with the same amount of normal saline. After that, the transcriptional levels of PEG2, COX-2, vascular endothelial growth factor (VEGF) and β-catenin in rats of the experimental group A, experimental group B and control group were detected via fluorescence quantitative Polymerase Chain Reaction (PCR) assay. Enzyme-linked immunosorbent assay (ELISA) and Western blotting were conducted to determine the changes in protein levels of PEG2, COX-2, VEGF and β-catenin in rats of the experimental group A, experimental group B and control group. The expression level of VEGF in bone tissues at fracture ends of rats in the experimental group A, experimental group B and control group was observed through the hematoxylin-eosin (HE) staining. Furthermore, micro-computed tomography (CT) was employed to evaluate callus formation. The transcriptional and translational levels of COX-2, β-catenin and VEGF in rats of experimental group A treated with COX-2 inhibitors were significantly down-regulated when compared with those of the control group, showing statistically significant differences (p<0.05). However, the levels of these genes were markedly elevated in the experimental group B treated with PGE2 in comparison with those in the control group, and the differences were statistically significant (p<0.05). After 6 weeks, HE staining showed that the expression level of VEGF in rats of the experimental group B was remarkably higher than that of the experimental group A (p<0.05). Micro-CT results revealed that the mean trabecular plate density (MTPD) of rats in the experimental group B (73.29±5.4) was markedly higher than the number of osteoblasts (49.6±3.9) in the experimental group A, showing a statistically significant difference (p<0.05). COX-2/PGE2 facilitates fracture healing by activating the Wnt/β-catenin signaling pathway.

Diabetes Perturbs Bone Microarchitecture and Bone Strength through Regulation of Sema3A/IGF-1/β-Catenin in Rats

Purpose: Increasing evidence supported that semaphorin 3A (Sema3A), insulin-like growth factor (IGF)-1 and β-catenin were involved in the development of osteoporosis and diabetes. This study is aimed to evaluate whether Sema3A/IGF-1/β-catenin is directly involved in the alterations of bone microarchitecture and bone strength of diabetic rats. Methods: Diabetic rats were induced by streptozotocin and high fat diet exposure. Bone microarchitecture and strength in the femurs were evaluated by micro-CT scanning, three-point bending examination and the stainings of HE, alizarin red S and safranin O/fast green, respectively. The alterations of lumbar spines microarchitecture were also determined by micro-CT scanning. Western blot and immunohistochemical analyses were used to examine the expression of Sema3A, β-catenin, IGF-1, peroxisome proliferator-activated receptor γ (PPARγ) and cathepsin K in rat tibias. Results: Diabetic rats exhibited decreased trabecular numbers and bone formation, but an increased trabecular separation in the femurs and lumbar spines. Moreover, the increased bone fragility and decreased bone stiffness were evident in the femurs of diabetic rats. Diabetic rats also exhibited a pronounced bone phenotype which manifested by decreased expression of Sema3A, IGF-1 and β-catenin, as well as increased expression of cathepsin K and PPARγ. Conclusions: This study suggests that diabetes could perturb bone loss through the Sema3A/IGF-1/β-catenin pathway. Sema3A deficiency in bone may contribute to upregulation of PPARγ and cathepsin K expression, which further disrupts bone remodeling in diabetic rats.