BACKGROUND AND PURPOSE: The wnt/β-catenin signaling pathway plays a critical role in embryonic development and adult-tissue homeostasis. Recent investigations implicate the importance of wnt/β-catenin signaling in normal wound healing and its sustained activation being associated with fibrogenesis. We investigated the immunolocalization and activation of wnt/β-catenin in polymyositis (PM), dermatomyositis (DM), and Duchenne muscular dystrophy (DMD). METHODS: Immunofluorescence staining and Western blot analysis of β-catenin were performed in muscle specimens from 6 PM, 8 DM, and 6 DMD subjects. The β-catenin/Tcf4 DNA-binding activity in muscle was studied using an electrophoretic mobility shift assay (EMSA), and serum wnt/β-catenin/Tcf transcriptional activity was measured using a luciferase reporter gene assay. RESULTS: Immunoreactivity for β-catenin was found in the cytoplasm and nuclei of muscle fibers in PM, DM, and DMD. The protein level of β-catenin was elevated, and EMSA analysis confirmed the activation of wnt/β-catenin signaling. The transcriptional activities of β-catenin/Tcf in the circulation were increased in patients with PM, DM, and DMD, especially in those with interstitial lung disease, and these transcriptional activities decreased when PM or DM patients exhibited obvious clinical improvements. CONCLUSIONS: Our findings indicate that wnt/β-catenin signaling is activated in PM, DM, and DMD. Its activation in muscle tissue and the circulation may play a role in modulating muscle regeneration and be at least partly involved in the process of muscle and pulmonary fibrosis.
Blotting, Western ; Cytoplasm ; Dermatomyositis* ; Electrophoretic Mobility Shift Assay ; Embryonic Development ; Female ; Fluorescent Antibody Technique ; Genes, Reporter ; Homeostasis ; Humans ; Luciferases ; Lung Diseases, Interstitial ; Muscular Dystrophy, Duchenne* ; Polymyositis* ; Pregnancy ; Pulmonary Fibrosis ; Regeneration ; Wound Healing

Portal hypertension is a common physiopathological change in liver cirrhosis. In this study, rabbits were used and the model of pre-hepatic portal hypertension (PHT) was induced by partial ligation of portal vein in two steps. We measured the diameters of portal vein and small mesenteric vein at different time-points. Then we detected the stress forces induced by blood flow in varicose veins and in portal vein; such forces included hydrostatic pressure, shear stress and circumferential stress. With the increase of the diameter of varicose small mesenteric vein, the hydrostatic pressure and circumferential stress gradually elevated and shear stress descended markedly in both the portal vein and the small mesenteric vein of PHT rabbits, between which there was a positive linear correlation. The findings in our study indicate that the complications of PHT are partially attributable to the environment of lower shear stress and higher circumferential stress in which the blood vessels of portal venous system live.
Animals ; Hemodynamics ; Hypertension, Portal ; etiology ; pathology ; physiopathology ; Mesenteric Veins ; pathology ; physiopathology ; Portal Vein ; pathology ; physiopathology ; Rabbits ; Stress, Mechanical ; Vascular Resistance ; physiology ; Venous Pressure