Gastroenterology
Volume 136, Issue 7 , Pages 2345-2355.e4 , June 2009

Fibronectin Stimulates Endothelin-1 Synthesis in Rat Hepatic Myofibroblasts via a Src/ERK-Regulated Signaling Pathway

Received 26 July 2008 ,Accepted 5 January 2009.

References 

  1. Jarnagin WR, Rockey DC, Koteliansky VE, et al. Expression of variant fibronectins in wound healing: cellular source and biological activity of the EIIIA segment in rat hepatic fibrogenesis. J Cell Biol. 1994;127:2037–2048
  2. Racine-Samson L, Rockey DC, Bissell DM. The role of α1β1 integrin in wound contraction (A quantitative analysis of liver myofibroblasts in vivo and in primary culture). J Biol Chem. 1997;272:30911–30917
  3. Zhou X, Murphy FR, Gehdu N, et al. Engagement of αvβ3 integrin regulates proliferation and apoptosis of hepatic stellate cells. J Biol Chem. 2004;279:23996–24006
  4. Rockey DC, Fouassier L, Chung JJ, et al. Cellular localization of endothelin-1 and increased production in liver injury in the rat: potential for autocrine and paracrine effects on stellate cells. Hepatology. 1998;27:472–480
  5. Rockey DC, Chung JJ. Endothelin antagonism in experimental hepatic fibrosis (Implications for endothelin in the pathogenesis of wound healing). J Clin Invest. 1996;98:1381–1388
  6. Marsen TA, Weber F, Egink G, et al. Cyclosporin A induces prepro endothelin-1 gene transcription in human endothelial cells. Eur J Pharmacol. 1999;379:97–106
  7. Xu D, Emoto N, Giaid A, et al. ECE-1: a membrane-bound metalloprotease that catalyzes the proteolytic activation of big endothelin-1. Cell. 1994;78:473–485
  8. Shao R, Shi Z, Gotwals PJ, et al. Cell and molecular regulation of endothelin-1 production during hepatic wound healing. Mol Biol Cell. 2003;14:2327–2341
  9. Yu Q, Shao R, Qian HS, et al. Gene transfer of the neuronal NO synthase isoform to cirrhotic rat liver ameliorates portal hypertension. J Clin Invest. 2000;105:741–748
  10. Rockey DC, Housset CN, Friedman SL. Activation-dependent contractility of rat hepatic lipocytes in culture and in vivo. J Clin Invest. 1993;92:1795–1804
  11. Miyazaki T, Sanjay A, Neff L, et al. Src kinase activity is essential for osteoclast function. J Biol Chem. 2004;279:17660–17666
  12. Pytela R, Pierschbacher MD, Ruoslahti E. Identification and isolation of a 140 kd cell surface glycoprotein with properties expected of a fibronectin receptor. Cell. 1985;40:191–198
  13. Shi-Wen X, Chen Y, Denton CP, et al. Endothelin-1 promotes myofibroblast induction through the ETA receptor via a rac/phosphoinositide 3-kinase/Akt-dependent pathway and is essential for the enhanced contractile phenotype of fibrotic fibroblasts. Mol Biol Cell. 2004;15:2707–2719
  14. Shao R, Rockey DC. Effects of endothelins on hepatic stellate cell synthesis of endothelin- 1 during hepatic wound healing. J Cell Physiol. 2002;191:342–350
  15. Reif S, Lang A, Lindquist JN, et al. The role of focal adhesion kinase-phosphatidylinositol 3-kinase-akt signaling in hepatic stellate cell proliferation and type I collagen expression. J Biol Chem. 2003;278:8083–8090
  16. Ruoslahti E. Integrins. J Clin Invest. 1991;87:1–5
  17. Milliano MT, Luxon BA. Initial signaling of the fibronectin receptor (α5β1 integrin) in hepatic stellate cells is independent of tyrosine phosphorylation. J Hepatol. 2003;39:32–37
  18. Nimmer D, Bergtrom G, Hirano H, et al. Regulation of plasma fibronectin biosynthesis by glucocorticoids in chick hepatocyte cultures. J Biol Chem. 1987;262:10369–10375
  19. Kennedy L, Shi-Wen X, Carter DE, et al. Fibroblast adhesion results in the induction of a matrix remodeling gene expression program. Matrix Biol. 2008;27:274–281
  20. Oh E, Pierschbacher M, Ruoslahti E. Deposition of plasma fibronectin in tissues. Proc Natl Acad Sci U S A. 1981;78:3218–3221
  21. Thompson PN, Cho E, Blumenstock FA, et al. Rebound elevation of fibronectin after tissue injury and ischemia: role of fibronectin synthesis. Am J Physiol. 1992;263:G437–G445
  22. Sieg DJ, Ilic D, Jones KC, et al. Pyk2 and Src-family protein-tyrosine kinases compensate for the loss of FAK in fibronectin-stimulated signaling events but Pyk2 does not fully function to enhance FAK- cell migration. EMBO J. 1998;17:5933–5947
  23. Schlaepfer DD, Hanks SK, Hunter T, et al. Integrin-mediated signal transduction linked to Ras pathway by GRB2 binding to focal adhesion kinase. Nature. 1994;372:786–791
  24. Pinzani M, Failli P, Ruocco C, et al. Fat-storing cells as liver-specific pericytes (Spatial dynamics of agonist-stimulated intracellular calcium transients). J Clin Invest. 1992;90:642–646
  25. Housset C, Rockey DC, Bissell DM. Endothelin receptors in rat liver: lipocytes as a contractile target for endothelin 1. Proc Natl Acad Sci U S A. 1993;90:9266–9270
  26. Rockey DC. Vascular mediators in the injured liver. Hepatology. 2003;37:4–12
  27. Woodsome TP, Polzin A, Kitazawa K, et al. Agonist- and depolarization-induced signals for myosin light chain phosphorylation and force generation of cultured vascular smooth muscle cells. J Cell Sci. 2006;119:1769–1780

 Conflicts of interest The authors disclose no conflicts.

 Funding Supported by the NIH (Grant R01 DK 50574 to D.C.R.).

PII: S0016-5085(09)00166-8

doi: 10.1053/j.gastro.2009.01.062

Gastroenterology
Volume 136, Issue 7 , Pages 2345-2355.e4 , June 2009

Article Tools

* Image Usage & Resolution