title: Cardiac stem cells transplantation enhances the expression of connexin 43 via the ANG II/AT1R/TGF-beta1 signaling pathway in a rat model of myocardial infarction.
abstract: BACKGROUND
  In this study, we hypothesized that CSCs mediated the expression of Cx43 after transplantation post MI via the ANG II/AT1R/TGF-beta1 signaling pathway.
  
  
  METHODS
  Myocardial infarction (MI) was induced in twenty male Sprague-Dawley rats. The rats were randomized into two groups and were then received the injection of 5 × 10(6) CSCs labeled with PKH26 in phosphate buffer solution (PBS) or equal PBS alone into the infarct anterior ventricular free wall two weeks after MI. Six weeks later, relevant signaling molecules involved were all examined.
  
  
  RESULTS
  In the CSCs group, an increased expression of Cx43 could be observed in different zones of the left ventricle (P<0.01). There was a significant reduction of the angiotensin II (ANG II) level in plasma and different regions of the left ventricular cardiac tissues (P<0.05; P<0.01). The angiotensin II type I receptor (AT1R) was decreased accompanied with an enhanced expression of angiotensin II type II receptor (AT2R) (P<0.01). Transforming growth factor beta-1(TGF-beta1) was downregulated (P<0.01). The expression of mothers against decapentaplegic homolog (SMAD) proteins including SMAD2 and SMAD3 was attenuated whereas SMAD7 was elevated (P<0.01, P<0.01, P<0.05). In addition, the expression of mitogen-activated protein kinases (MAPKs) including extracellular kinases 1/2 (ERK1/2) and p38 was also found to be reduced (P<0.01).
  
  
  CONCLUSIONS
  CSCs transplantation could enhance the level of Cx43 after MI. They might function through intervening the ANGII/AT1R/TGF-beta1 signaling pathway to regulate the expression of Cx43.
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong 510120, China; Department of Emergency, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong, China.
authors.forename: Jingying
authors.initials: J
authors.lastname: Hou
authors.affiliation: The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Xi Road, Guangzhou, Guangdong, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yan
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong 510120, China; Department of Emergency, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong, China.
authors.forename: Tianzhu
authors.initials: T
authors.lastname: Guo
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong 510120, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Xing
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong 510120, China; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, 107 Yanjiang Xi Road, Guangzhou, Guangdong, China.
authors.forename: Shaoxin
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong 510120, China; Department of Emergency, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong, China.
authors.forename: Changqing
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong 510120, China; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, 107 Yanjiang Xi Road, Guangzhou, Guangdong, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Huang
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong 510120, China; Department of Emergency, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong, China.
authors.forename: Huibao
authors.initials: H
authors.lastname: Long
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong 510120, China; The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Xi Road, Guangzhou, Guangdong, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhong
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong 510120, China; Department of Emergency, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong, China.
authors.forename: Quanhua
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong 510120, China; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, 107 Yanjiang Xi Road, Guangzhou, Guangdong, China.
authors.forename: Jingfeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong 510120, China; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, 107 Yanjiang Xi Road, Guangzhou, Guangdong, China; Department of Emergency, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong, China. Electronic address: tongwang316@163.com.
authors.forename: Tong
authors.initials: T
authors.lastname: Wang
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D018031:Connexin 43 / Q000096:biosynthesis*; D004195:Disease Models, Animal; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000637:transplantation*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D033581:Stem Cell Transplantation / Q000379:methods*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D018031:Connexin 43; C580592:Gja1 protein, rat; D044140:Receptor, Angiotensin, Type 1; D053773:Transforming Growth Factor beta1; D000804:Angiotensin II
keywords: Angiotensin II; Cardiac stem cells; Connexin 43; Mitogen-activated protein kinases; Mothers against decapentaplegic homolog; Myocardial infarction; Transforming growth factor beta-1