title: Role of protein kinase C β₂ in relaxin-mediated inhibition of cardiac fibrosis.
abstract: BACKGROUND
  Relaxin is a pleiotropic hormone owing endogenous antifibrosis effect on numerous organs. We demonstrated relaxin's inhibitive effect on cardiac fibrosis previously.
  
  
  OBJECTIVE
  The aim of this study was to investigate the role of protein kinase C (PKC) β2 in relaxin's action under high glucose conditions.
  
  
  RESULTS
  Cardiac fibroblasts (CFs) were isolated, exposed to high glucose and incubated with recombinant human relaxin (rhRLX). Western blot analysis revealed a relaxin-mediated decrease in total expression and translocation of PKCβ2, showing downregulation of PKCβ2 is involved in relaxin's action. Blocking PKCβ2 pathway with ruboxistaurin accelerated rhRLX-mediated inhibition in both proliferation of CFs and deposition of collagen.
  
  
  CONCLUSIONS
  In conclusion, relaxin can inhibit high glucose-associated cardiac fibrosis partly through PKCβ2 pathway. Further work should be done to fully understand intracellular mechanisms of relaxin's action to accelerate its clinical use.
authors.affiliation: Department of Cardiology, Beijing Friendship Hospital, Capital Medical University, No. 95, Yongan Road, Xicheng District, Beijing, 100050, People's Republic of China.
authors.forename: W
authors.initials: W
authors.lastname: Su
authors.forename: P
authors.initials: P
authors.lastname: Wang
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.forename: H
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005355:Fibrosis / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D064546:Protein Kinase C beta / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012065:Relaxin / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; C099154:ruboxistaurin; D012065:Relaxin; D064546:Protein Kinase C beta; D005947:Glucose
references.citation: Circ Heart Fail. 2013 Jul;6(4):711-8
references.pmid: 23625945
references.citation: Proc Natl Acad Sci U S A. 1991 May 1;88(9):3997-4000
references.pmid: 1850844
references.citation: J Am Coll Cardiol. 2001 Jun 1;37(7):1943-9
references.pmid: 11401136
references.citation: Ann N Y Acad Sci. 1985;460:246-57
references.pmid: 3914229
references.citation: Mol Cell Endocrinol. 2012 Nov 5;363(1-2):46-61
references.pmid: 22835547
references.citation: Am J Physiol Cell Physiol. 2011 Aug;301(2):C304-15
references.pmid: 21525431
references.citation: Am J Physiol Heart Circ Physiol. 2009 Jul;297(1):H29-36
references.pmid: 19429819
references.citation: Vasc Health Risk Manag. 2008;4(3):575-96
references.pmid: 18827908
references.citation: Curr Drug Saf. 2011 Nov 1;6(5):324-8
references.pmid: 22424540
references.citation: Cardiovasc Res. 2007 Mar 1;73(4):770-82
references.pmid: 17250813
references.citation: Med Sci Monit. 2012 Feb;18(2):BR69-75
references.pmid: 22293869
references.citation: Diabetes. 2013 Jul;62(7):2318-28
references.pmid: 23474486
references.citation: Endocrinology. 2004 Sep;145(9):4125-33
references.pmid: 15155573
references.citation: J Cell Mol Med. 2012 Mar;16(3):507-19
references.pmid: 21554533
references.citation: J Endocrinol Invest. 2009 Mar;32(3):242-7
references.pmid: 19542742
references.citation: Circulation. 1999 Jan 26;99(3):384-91
references.pmid: 9918525
references.citation: Mol Cell Endocrinol. 1989 Oct;66(2):251-5
references.pmid: 2612734
references.citation: Endocrinology. 2008 Jul;149(7):3286-93
references.pmid: 18388190
references.citation: Endocrinology. 1980 Sep;107(3):691-8
references.pmid: 7398575
references.citation: J Am Coll Cardiol. 2006 Feb 21;47(4):693-700
references.pmid: 16487830
references.citation: Biochem J. 1999 Oct 15;343 Pt 2:443-52
references.pmid: 10510312
references.citation: Diabetes Metab Res Rev. 2004 Jan-Feb;20(1):28-43
references.pmid: 14737743
references.citation: J Endocrinol Invest. 2011 Nov;34(10):e369-73
references.pmid: 22067223
references.citation: Diabetologia. 2001 Apr;44(4):480-7
references.pmid: 11357479
references.citation: Clin Sci (Lond). 2012 Feb;122(4):161-73
references.pmid: 21892921
references.citation: Am Heart J. 2012 Oct;164(4):530-7
references.pmid: 23067911
references.citation: Biochem Biophys Res Commun. 2007 Dec 14;364(2):231-7
references.pmid: 17942077
references.citation: Circ J. 2012;76(4):943-9
references.pmid: 22313801
references.citation: Br J Pharmacol. 1999 May;127(1):91-8
references.pmid: 10369460
references.citation: J Lab Clin Med. 2000 Apr;135(4):316-23
references.pmid: 10779047
references.citation: Lab Invest. 2011 May;91(5):675-90
references.pmid: 21221074
references.citation: Retina. 2011 Nov;31(10):2084-94
references.pmid: 21862954