Xiao-Hui Xi1, Yan Wang2, Jun Li2, Fu-Wen Wang2, Gui-Hong Tian2, Mao-Shan Yin1, Yan-Ling Mu3, Zhao-Zhong Chong2. 1. Key Laboratory for Rare Disease of Shandong Province, Department of Pharmacology, Institute of Materia Medica, Shandong Academy of Medical Sciences, Jinan, 250062, China; School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, 250062, China. 2. Key Laboratory for Rare Disease of Shandong Province, Department of Pharmacology, Institute of Materia Medica, Shandong Academy of Medical Sciences, Jinan, 250062, China. 3. Key Laboratory for Rare Disease of Shandong Province, Department of Pharmacology, Institute of Materia Medica, Shandong Academy of Medical Sciences, Jinan, 250062, China. Electronic address: myling501@hotmail.com.
Abstract
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.
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.
Authors: Aurelija Abraityte; Ida G Lunde; Erik T Askevold; Annika E Michelsen; Geir Christensen; Pål Aukrust; Arne Yndestad; Arnt Fiane; Arne Andreassen; Svend Aakhus; Christen P Dahl; Lars Gullestad; Kaspar Broch; Thor Ueland Journal: Sci Rep Date: 2017-06-14 Impact factor: 4.379