AJP - Regulatory, Integrative and Comparative Physiology, Vol 272, Issue 6 1960-R1965, Copyright © 1997 by American Physiological Society

ARTICLES

Dysregulated proteolytic balance as the basis of excess extracellular matrix in fibrotic disease

C. A. Peters, M. R. Freeman, C. A. Fernandez, J. Shepard, D. G. Wiederschain and M. A. Moses
Department of Urology, Children's Hospital, Boston, Massachusetts, USA.

To investigate mechanisms of tissue fibrosis, we developed a model of ovine fetal bladder fibrosis due to surgically induced obstruction. Tissues were analyzed for matrix metalloproteinases (MMPs) and their inhibitors, the tissue inhibitors of metalloproteinases (TIMPs). Active MMP-2 was not detected in obstructed bladders, while latent and active forms were detected in normal bladders. MMP-1 (interstitial collagenase) activity was lower in obstructed bladders. MMP inhibitory activity was increased with obstruction, as were levels of TIMP mRNA and protein. These results indicate that the proteins responsible for collagen degradation are present in the developing bladder, and a shift in the proteolytic balance favoring inhibition of degradation occurs in a model of obstruction-induced fibrosis. This altered proteolytic balance favors accumulation of extracellular matrix and decreased tissue compliance characteristic of this and perhaps other fibrotic conditions.

This article has been cited by other articles:

				M. Imamura, A. Kanematsu, S. Yamamoto, Y. Kimura, I. Kanatani, N. Ito, Y. Tabata, and O. Ogawa Basic fibroblast growth factor modulates proliferation and collagen expression in urinary bladder smooth muscle cells Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1007 - F1017. [Abstract] [Full Text] [PDF]

				N. Thiruchelvam, P. Nyirady, D. M. Peebles, C. H. Fry, P. M. Cuckow, and A. S. Woolf Urinary Outflow Obstruction Increases Apoptosis and Deregulates Bcl-2 and Bax Expression in the Fetal Ovine Bladder Am. J. Pathol., April 1, 2003; 162(4): 1271 - 1282. [Abstract] [Full Text] [PDF]

				U. A. Stock, T. Sakamoto, S. Hatsuoka, D. P. Martin, M. Nagashima, A. M. Moran, M. A. Moses, P. N. Khalil, F. J. Schoen, J. P. Vacanti, et al. Patch augmentation of the pulmonary artery with bioabsorbable polymers and autologous cell seeding J. Thorac. Cardiovasc. Surg., December 1, 2000; 120(6): 1158 - 1167. [Abstract] [Full Text] [PDF]

				J. Fang, Y. Shing, D. Wiederschain, L. Yan, C. Butterfield, G. Jackson, J. Harper, G. Tamvakopoulos, and M. A. Moses Matrix metalloproteinase-2 is required for the switch to the angiogenic phenotype in a tumor model PNAS, April 11, 2000; 97(8): 3884 - 3889. [Abstract] [Full Text] [PDF]

				J. M. Park, R. M. Adam, C. A. Peters, P. D. Guthrie, Z. Sun, M. Klagsbrun, and M. R. Freeman AP-1 mediates stretch-induced expression of HB-EGF in bladder smooth muscle cells Am J Physiol Cell Physiol, August 1, 1999; 277(2): C294 - C301. [Abstract] [Full Text] [PDF]