title: Epigallocatechin gallate attenuated the activation of rat cardiac fibroblasts induced by angiotensin II via regulating β-arrestin1.
abstract: OBJECTIVE
  Angiotensin II (AngII) activated cardiac fibroblasts (CFs) predominantly through AngII subtype 1a receptor (AT1aR). This study was carried out to explore the potential inhibitory effects and mechanisms of epigallocatechin gallate (EGCG) on AngII induced rat CFs.
  
  
  METHODS
  Viability, proliferation and collagen production of CFs were measured by MTT assay, [3H]-thymidine and [3H]-proline incorporation respectively. β-arrestin1 (βarr1), AT1aR and AT1bR mRNA levels were determined by quantitative PCR. AT1R, Gq, βarr 1/2, phosphorylated kinase C (p-PKC)-delta expressions were detected by western blotting. We blocked βarr1 expression using βarr1 small interfering RNA (siRNA).
  
  
  RESULTS
  EGCG inhibited the activation of CFs induced by AngII. βarr1 mRNA level revealed a positive correlation with the viability of CFs. SiRNA targeting βarr1 blocked the activation of CFs. In vitro, AngII increased βarr1 mRNA, total and membrane βarr1 protein expressions, but reduced AT1aR mRNA, global and membrane AT1R, total Gq and cytoplasmic p-PKC-delta levels. Administration of EGCG restored the above abnormalities, whereas Gq levels were not affected.
  
  
  CONCLUSIONS
  Our findings showed that βarr1 is essential for AngII-mediated activation of CFs. EGCG attenuated CFs activation induced by AngII via regulating βarr1 and thus, modulating AT1aR mediated signaling.
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong, China.
authors.forename: Yong-Sheng
authors.initials: YS
authors.lastname: Han
authors.forename: Lei
authors.initials: L
authors.lastname: Lan
authors.forename: Jun
authors.initials: J
authors.lastname: Chu
authors.forename: Wei-Qiang
authors.initials: WQ
authors.lastname: Kang
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Ge
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D019390:Arrestins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism; D009206:Myocardium / Q000166:cytology; D051745:Protein Kinase C-delta / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; D034741:RNA, Small Interfering; D044140:Receptor, Angiotensin, Type 1; D000071557:beta-Arrestins; D000804:Angiotensin II; D002392:Catechin; D003094:Collagen; C045651:epigallocatechin gallate; D051745:Protein Kinase C-delta; D043802:GTP-Binding Protein alpha Subunits, Gq-G11