Arginine vasopressin stimulates proliferation of adult rat cardiac fibroblasts via protein kinase C-extracellular signal-regulated kinase 1/2 pathway

( views:79, downloads:0 )
Author:
HE Yan-Ping(Department of Cardiology, Tangdu Hospital, the Fourth Military Medical University, Xi'an 710038, China)
ZHAO Lian-You(Department of Cardiology, Tangdu Hospital, the Fourth Military Medical University, Xi'an 710038, China)
ZHENG Qiang-Sun(Department of Cardiology, Tangdu Hospital, the Fourth Military Medical University, Xi'an 710038, China)
LIU Shao-Wei(Department of Cardiology, Tangdu Hospital, the Fourth Military Medical University, Xi'an 710038, China)
ZHAO Xiao-Yan(Department of Cardiology, Tangdu Hospital, the Fourth Military Medical University, Xi'an 710038, China)
LU Xiao-Long(Department of Cardiology, Tangdu Hospital, the Fourth Military Medical University, Xi'an 710038, China)
NIU Xiao-Lin(Department of Cardiology, Tangdu Hospital, the Fourth Military Medical University, Xi'an 710038, China)
Journal Title:
ACTA PHYSIOLOGICA SINICA
Issue:
Volume 60, Issue 03, 2008
DOI:
Key Word:
arginine vasopressin;V1 receptor;extracellular sigual-regulated kinase 1/2;protein kinase C;p27Klp1;cyclin;cardiac fibroblast

Abstract: Arginine vasopressin (AVP), a neurohormone and hemodynamic factor implicated in the pathophysiology of hypertension and congestive heart failure, can also act as a growth-stimulating factor. Our previous work demonstrated that AVP is a mitogen for neonatal rat cardiac fibroblasts (CFs). In the present study, we extended our investigations to adult rat CFs to explore whether AVP could induce adult rat CF proliferation and, if so, to identify the mechanism involved. Adult rat CFs were isolated, cultured and subjected to AVP treatment. DNA synthesis and cell cycle distribution were analyzed by [3H]-thymidine incorporation and flow cytometry. Cellular extracellular signal-regulated kinase 1/2 (ERK 1/2) activity was measured by in vitro kinase assay using myelin basic protein (MBP) as a substrate. Protein expressions of total-and phospho-ERK1/2, p27Kip1, cyclins D1, A, E were assessed by Western blot. The results showed that AVP stimulated DNA synthesis in adult rat CFs, and the effect was abolished by a V1 receptor antagonist, d(CH2)5[Tyr2(Me),Arg8-vasopressin (0.1μmol/L), but not by a V2 receptor antagonist, desglycinamide-[d(CH2)5, D-Ile2, Ile4, Arg8-vasopressin (0.1μmol/L). AVP induced an activation of ERK1/2, which could be mimicked by the protein kinase C (PKC) activator, phorbol 12-myfistate 13-acetate (PMA, 30nmol/L, 5min), but abolished by depiction of PKC via chronic PMA incubation (2.5μmol/L,24h). In addition, AVP down-regulated protein expression of p27Kip1, increased protein expressions of cyclins D1, A and E, and induced cell cycle progression from G0/G1 into S stage. Inhibition of ERK1/2 activation by PD98059 (30μmol/L) abolished the effect of AVP on DNA synthesis, protein expressions of p27Klp1, cyclins D1, A and E as well as cell cycle progression. These results suggest that AVP is also a growth factor for adult rat CFs. The mitogenic effect of AVP is mediated via V1 receptors and PKC-ERK 1/2 pathway. Moreover, AVP modulates the expressions of cell cycle regulatory proteins p27Kip1 and cyclins D1, A and E, which lie downstream of ERK 1/2 activation, and induces cell cycle progression in adult rat CFs.

  • [1]Cohn JN,Ferrari R,Sharpe N.Cardiac remodeling-concepts and clinical implications:a consensus paper from an international forum on cardiac remodeling.Behalf of an International Forum on Cardiac Remodeling.J Am Coll Cardiol 2000;35(3):569-582.
  • [2]Weber KT,Brilla CG,Janicki JS.Myocardial fibrosis:functional significance and regulatory factors.Cardiovasc Res 1993;27(3):341-348.
  • [3]Yang F,Liu YH,Yang XP,Xu J,Kapke A,Carretero OA.Myocardial infarction and cardiac remodelling in mice.Exp Physiol 2002;87(5):547-555.
  • [4]McNeill JR.Role of vasopressin in the control of arterial pressure.Can J Physiol Pharmacol 1983;61(11):1226-1235.
  • [5]Uretsky BF,Verbalis JG,Generalovich T,Valdes A,Reddy PS.Plasma vasopressin response to osmotic and hemodynamic stimuli in heart failure.Am J Physiol 1985;248(3Pt2):H396-H402.
  • [6]Chatterjee K.Neurohormonal activation in congestive heart failure and the role of vasopressin.Am J Cardiol 2005;95(9A):8B-13B.
  • [7]Tahara A,Tsukada J,Tomura Y,Suzuki T,Yatsu T,Shibasaki M.Effect of YM218,a nonpeptide vasopressin V (1A) receptor-selective antagonist,on rat mesangial cell hyperplasia and hypertrophy.Vascul Pharmacol 2007;46(6):463-469.
  • [8]Bhora FY,Kothary PC,Imanishi H,Eckhauser FE,Raper SE.Vasopressin stimulates DNA synthesis in cultured rat hepatocytes.J Surg Res 1994;57(6):706-710.
  • [9]Lagumdzija A,Pernow Y,Bucht E,Gonon APetersson M.The effects of arg-vasopressin on osteoblast-like cells in endothelial nitric oxide synthase-knockout mice and their wild type counterparts.Peptides 2005;26(9):1661-1666.
  • [10]Chiu T,Wu SS,Santiskulvong C,Tangkijvanich P,Yee HF Jr,Rozengurt E.Vasopressin-mediated mitogenic signaling in intestinal epithelial cells.Am J Physiol Cell Physiol 2002;282(3):C434-C450.
  • [11]Fan YH(范延红),Zhao LY,Zheng QS,Xue YS,Yang XD,Tian JW,Xu L.Arginine vasopressin-induced nitric oxide content changes in cultured cardiac fibroblasts and its relation to nuclear factor-κB.Acta Physiol Sin(生理学报)2003;55:417-421 (Chinese,English abstract).
  • [12]Yang XD,Zhao LY,Zheng QS,Li X.Effects of arginine vasopressin on growth of rat cardiac fibroblasts:role of V1 receptor.J Cardiovasc Pharmacol 2003;42(1):132-135.
  • [13]Lazou A,Bogoyevitch MA,Clerk A,Fuller SJ,Marshall CJ,Sugden PH.Regulation of mitogen-activated protein kinase cascade in adult rat heart preparations in vitro.Circ Res 1994;75(5):932-941.
  • [14]Chen D,Fong HW,Davis JS.Induction of c-fos and c-jun messenger ribonucleic acid expression by prostaglandin F2α is mediated by a protein kinase C-dependent extracellular signal-regulated kinase mitogen-activated protein kinase pathway in bovine luteal cells.Endocrinology 2001;142(2):887-895.
  • [15]Rouleau JL,Packer M,Moye L,de Champlain J,Bichet D,Klein M,Rouleau JR,Sussex B,Arnold JM,Sestier F,et al.Prognostic value of neurohumoral activation in patients with an acute myocardial infarction:effeet of captopril.J Am Coll Cardiol 1994;24(3):583-591.
  • [16]Nakamura Y,Haneda T,Osaki J,Miyata S,Kikuchi K.Hypertrophic growth of cultured neonatal rat heart cells mediated by vasopressin V (1A) receptor.Eur J Pharmacol 2000:391(1-2):39-48.
  • [17]Fukuzawa J,Haneda T,Kikuchi K.Arginine vasopressin increases the rate of protein synthesis in isolated perfused adult rat heart via the V1 receptor.Mol Cell Biochem 1999;195(1-2):93-98.
  • [18]Tahara A,Tomura Y,Wada K,Kusayama T,Tsukada J,Ishii N,Yatsu T,Uchida W,Tanaka A.Effect of YM087,a potent nonpeptide vasopressin antagonist,on vasopressin-induced protein synthesis in neonatal rat cardiomyocyte.Cardiovasc Res 1998;38(1):198-205.
  • [19]Brown RD,Ambler SK,Mitchell MD,Long CS.The cardiac fibroblast:therapeutic target in myocardial remodeling and failure.Anna Rev Pharmacol Toxicol 2005:45:657-687.
  • [20]Xu YJ,Ouk Kim S,Liao DF,Katz S,Pelech SL.Stimulation of 90-and 70-kDa ribosomal protein S6 kinases by arginine vasopressin and lysophosphatidic acid in rat cardiomyocytes.Biochem Pharmacol 2000;59(9):1163-1171.
  • [21]Aharonovitz O,Aboulafia-Etzion S,Leor J,Alexander B,Granot Y.Stimulation of 42/44 kDa mitogen-activated protein kinases by arginine vasopressin in rat cardiomyocytes.Biochim Biophys Acta Mol Cell Res 1998;1401(1):105-111.
  • [22]Kim K,Nose K,Shibanuma M.Significance of nuclear relocalization of ERK1/2 in reactivation of c-fos transcription and DNA synthesis in senescent fibroblasts.J Biol Chem 2000:275(27):20685-20692.
  • [23]Nofer JR,Junker R,Pulawski E,Fobker M,Levkau B,von Eckardstein A,Seedorf U,Assnann G,Walter M.High density lipoproteins induce cell cycle entry in vascular smooth muscle cells via mitogen activated protein kinase-dependent pathway.Thromb Haemost 2001;85(4):730-735.
  • [24]Lavoie JN,L' Allemain G,Brunet A,Muller & Pouyssegur J.Cyclin D1 expression is regulated positively by the p42/p44MAPK and negatively by the p38/HOGMAPK pathway.J Biol Chem 1996;271(34):20608-20616.
  • [25]Coats S,Flanagan WM,Nourse J,Roberts JM.Requirement of p27Kip1 for restriction point control of the fibroblast cell cycle.Science 1996:272(5263):877-880.
  • [26]Bhatt KV,Spofford LS,Aram G,McMullen M,Pumiglia K,Aptin AE.Adhesion control of cyclin D1 and p27Kip1 levels is deregulated in melanoma cells through BRAF-MEK-ERK signaling.Oncogene 2005;24(21):3459-3471.
  • [27]Foster JS,Fernando RI,Ishida N,Nakayama KI,Wimalasena J.Estrogens down-regulate p27Kip1 in breast cancer cells through Skp2 and through nuclear export mediated by the ERK pathway.J Biol Chem 2003;278(42):41355-41366.
  • [28]Kortylewski M,Heinrich PC,Kauffmann ME,Bohm M,MacKiewicz A,Behrmann I.Mitogen-activated protein kinases control p27/Kip1 expression and growth of human melanoma cells.Biochem J 2001;357(Pt 1):297-303.
  • [29]Girard F,Strausfeld U,Fernandez A,Lamb NJ.Cyclin A is required for the onset of DNA replication in mammalian fibroblasts.Cell 1991;67(6):1169-1179.
WanfangData CO.,Ltd All Rights Reserved
About WanfangData | Contact US
Healthcare Department, Fuxing Road NO.15, Haidian District Beijing, 100038 P.R.China
Tel:+86-010-58882616 Fax:+86-010-58882615 Email:yiyao@wanfangdata.com.cn