title: Inhibition of lectin-like oxidized low-density lipoprotein receptor-1 reduces cardiac fibroblast proliferation by suppressing GATA Binding Protein 4.
abstract: Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and GATA Binding Protein 4 (GATA4) are important for the growth of cardiac fibroblasts (CFs). When deregulated, LOX-1 and GATA4 can cause cardiac remodeling. In the present study, we found novel evidence that GATA4 was required for the LOX-1 regulation of CF proliferation. The inhibition of LOX-1 by RNA interference LOX-1 lentivirus resulted in the loss of PI3K/Akt activation and GATA4 protein expression. The overexpression of LOX-1 by lentivirus rescued CF proliferation, PI3K/Akt activation, and GATA4 protein expression. Moreover, GATA4 overexpression enhanced CF proliferation with LOX-1 inhibition. We also found that the inhibition of PI3K/Akt activation by LY294002, a PI3K inhibitor, reduced cell proliferation and protein level of GATA4. In summary, GATA4 may play an important role in the LOX-1 and PI3K/Akt regulation of CF proliferation.
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Guangzhou Institute of Cardiovascular Disease, Guangzhou, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Guangzhou Institute of Cardiovascular Disease, Guangzhou, China.
authors.forename: Ning-Ning
authors.initials: NN
authors.lastname: Liu
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Guangzhou Institute of Cardiovascular Disease, Guangzhou, China.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Liu
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Guangzhou Institute of Cardiovascular Disease, Guangzhou, China.
authors.forename: Shuang-Wei
authors.initials: SW
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Guangzhou Institute of Cardiovascular Disease, Guangzhou, China.
authors.forename: Jing-Zhi
authors.initials: JZ
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Guangzhou Institute of Cardiovascular Disease, Guangzhou, China.
authors.forename: Ai-Qun
authors.initials: AQ
authors.lastname: Li
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Guangzhou Institute of Cardiovascular Disease, Guangzhou, China. Electronic address: gzliushiming@126.com.
authors.forename: Shi-Ming
authors.initials: SM
authors.lastname: Liu
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D050991:GATA4 Transcription Factor / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D051127:Scavenger Receptors, Class E / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D050991:GATA4 Transcription Factor; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051127:Scavenger Receptors, Class E; C084365:Gata4 protein, rat; C495136:OLR1 protein, rat
keywords: Cardiac fibroblasts; Cell proliferation; GATA Binding Protein 4; Lectin-like oxidized low-density lipoprotein receptor-1