| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on February 18, 2004
Accepted on May 10, 2004
Howard Florey Institute of Experimental Physiology and Medicine (C.S.S., I.M., R.A.D.B., S.L.L., G.W.T.), University of Melbourne, Victoria 3010, Australia; Connetics Corporation (E.N.U., J.M.), Palo Alto, CA 94303; and Baker Heart Research Institute (X.D.), Melbourne, Victoria 8008, Australia
* To whom correspondence should be addressed. E-mail: c.samuel{at}hfi.unimelb.edu.au.
Cardiac fibrosis is a key component of heart disease, and involves the proliferation and differentiation of matrix-producing fibroblasts. The effects of an anti-fibrotic peptide hormone, relaxin, in inhibiting this process were investigated. We used rat atrial and ventricular fibroblasts, which respond to pro-fibrotic stimuli and express the relaxin receptor (LGR7), in addition to two in vivo models of cardiac fibrosis. Cardiac fibroblasts when plated at low-density or stimulated with transforming growth factor-
(TGF-) or Angiotensin II (Ang II) accelerated fibroblast differentiation into myofibroblasts, as demonstrated by significantly increased 
-smooth muscle actin (-SMA) expression, collagen synthesis and collagen deposition (by up to 95% with TGF- and 40% with Ang II; all P < 0.05). Fibroblast proliferation was significantly increased by 10-8 M and 10-7 M Ang II (63-75%; P < 0.01) or 0.1-1 µg/ml insulin growth factor I (IGF-I; 27-40%; P < 0.05). Relaxin alone had no marked effect on these parameters, but significantly inhibited Ang II- and IGF-I-mediated fibroblast proliferation (by 15-50%) and Ang II- and TGF--mediated fibroblast differentiation, as detected by decreased expression of -SMA (by 65-88%) and collagen (by 60-80%). Relaxin also increased matrix metalloproteinase-2 expression in the presence of TGF- (P < 0.01) and Ang II (P < 0.05). Furthermore, relaxin decreased collagen overexpression when administered to two models of established fibrotic cardiomyopathy, one due to relaxin-deficiency (by 40%; P < 0.05) and the other to cardiac-restricted overexpression of 2-adrenergic receptors (by 58%; P < 0.01). These coherent findings indicate that relaxin regulates fibroblast proliferation, differentiation and collagen deposition and may have therapeutic potential in diseased states characterized by cardiac fibrosis.
This article has been cited by other articles:
 |
|
 |
|
  C. S. Samuel, T. D. Hewitson, Y. Zhang, and D. J. Kelly Relaxin Ameliorates Fibrosis in Experimental Diabetic Cardiomyopathy Endocrinology, July 1, 2008; 149(7): 3286 - 3293. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Xu, E. D. Lekgabe, X.-M. Gao, Z. Ming, G. W. Tregear, A. M. Dart, R. A. D. Bathgate, C. S. Samuel, and X.-J. Du Endogenous Relaxin Does Not Affect Chronic Pressure Overload-Induced Cardiac Hypertrophy and Fibrosis Endocrinology, February 1, 2008; 149(2): 476 - 482. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-l. Moore, S.-l. Tan, C.-y. Lo, L. Fang, Y.-D. Su, X.-M. Gao, E. A. Woodcock, R. J. Summers, G. W. Tregear, R. A. D. Bathgate, et al. Relaxin Antagonizes Hypertrophy and Apoptosis in Neonatal Rat Cardiomyocytes Endocrinology, April 1, 2007; 148(4): 1582 - 1589. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Jeyabalan, J. Novak, K. D. Doty, J. Matthews, M. C. Fisher, L. J. Kerchner, and K. P. Conrad Vascular Matrix Metalloproteinase-9 Mediates the Inhibition of Myogenic Reactivity in Small Arteries Isolated from Rats after Short-Term Administration of Relaxin Endocrinology, January 1, 2007; 148(1): 189 - 197. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. D. Lekgabe, S. G. Royce, T. D. Hewitson, M. L. K. Tang, C. Zhao, X. L. Moore, G. W. Tregear, R. A. D. Bathgate, X.-J. Du, and C. S. Samuel The Effects of Relaxin and Estrogen Deficiency on Collagen Deposition and Hypertrophy of Nonreproductive Organs Endocrinology, December 1, 2006; 147(12): 5575 - 5583. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Bathgate, R. Ivell, B. M. Sanborn, O. D. Sherwood, and R. J. Summers International Union of Pharmacology LVII: Recommendations for the Nomenclature of Receptors for Relaxin Family Peptides. Pharmacol. Rev., March 1, 2006; 58(1): 7 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. S. Samuel Relaxin: Antifibrotic Properties and Effects in Models of Disease Clin. Med. Res., November 1, 2005; 3(4): 241 - 249. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. O. Debrah, K. P. Conrad, A. Jeyabalan, L. A. Danielson, and S. G. Shroff Relaxin Increases Cardiac Output and Reduces Systemic Arterial Load in Hypertensive Rats Hypertension, October 1, 2005; 46(4): 745 - 750. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. D. Lekgabe, H. Kiriazis, C. Zhao, Q. Xu, X. L. Moore, Y. Su, R. A.D. Bathgate, X.-J. Du, and C. S. Samuel Relaxin Reverses Cardiac and Renal Fibrosis in Spontaneously Hypertensive Rats Hypertension, August 1, 2005; 46(2): 412 - 418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. T. Nguyen and C. W. Dessauer Relaxin Stimulates Protein Kinase C {zeta} Translocation: Requirement for Cyclic Adenosine 3',5'-Monophosphate Production Mol. Endocrinol., April 1, 2005; 19(4): 1012 - 1023. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Formigli, F. Francini, A. Tani, R. Squecco, D. Nosi, L. Polidori, S. Nistri, L. Chiappini, V. Cesati, A. Pacini, et al. Morphofunctional integration between skeletal myoblasts and adult cardiomyocytes in coculture is favored by direct cell-cell contacts and relaxin treatment Am J Physiol Cell Physiol, April 1, 2005; 288(4): C795 - C804. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
