title: Activation of Wnt/β-catenin/GSK3β signaling during the development of diabetic cardiomyopathy.
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.
  
  
  CONCLUSIONS
  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.affiliation: 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.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Xi
authors.affiliation: Key Laboratory for Rare Disease of Shandong Province, Department of Pharmacology, Institute of Materia Medica, Shandong Academy of Medical Sciences, Jinan, 250062, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory for Rare Disease of Shandong Province, Department of Pharmacology, Institute of Materia Medica, Shandong Academy of Medical Sciences, Jinan, 250062, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory for Rare Disease of Shandong Province, Department of Pharmacology, Institute of Materia Medica, Shandong Academy of Medical Sciences, Jinan, 250062, China.
authors.forename: Fu-Wen
authors.initials: FW
authors.lastname: Wang
authors.affiliation: Key Laboratory for Rare Disease of Shandong Province, Department of Pharmacology, Institute of Materia Medica, Shandong Academy of Medical Sciences, Jinan, 250062, China.
authors.forename: Gui-Hong
authors.initials: GH
authors.lastname: Tian
authors.affiliation: 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.
authors.forename: Mao-Shan
authors.initials: MS
authors.lastname: Yin
authors.affiliation: 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.
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Mu
authors.affiliation: Key Laboratory for Rare Disease of Shandong Province, Department of Pharmacology, Institute of Materia Medica, Shandong Academy of Medical Sciences, Jinan, 250062, China.
authors.forename: Zhao-Zhong
authors.initials: ZZ
authors.lastname: Chong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D058065:Diabetic Cardiomyopathies / Q000378:metabolism* / Q000473:pathology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D007150:Immunohistochemistry; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D060449:Wnt Signaling Pathway / Q000502:physiology*
chemical_list: D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3
keywords: Diabetic cardiomyopathy; GSK3β; Myocardial injury; Wnt2; β-Catenin