| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Medical Pharmacology and Toxicology, College of Medicine, Texas A&M University System Health Science Center, College Station, Texas, USA
2 Department of Veterinary Integrated Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, Texas, none
* To whom correspondence should be addressed. E-mail: parrish{at}medicine.tamhsc.edu.
Ischemia is a leading cause of acute renal failure (ARF), a disease associated with high morbidity and mortality. Disruption of intercellular adhesion in the proximal tubules is linked to ARF, although the molecular mechanism(s) remain unclear. Our previous studies have shown that ischemia is associated with cadherin cleavage and loss in NRK cells, putatively due to a matrix metalloproteinase (MMP) (7). In the current studies, a MMP required for E-cadherin cleavage and N-cadherin loss was identified. Chemical inhibitors against a number of soluble MMPs (1, 2, 3, 8, 9) failed to completely attenuate ischemia-induced cadherin loss. Under ischemic conditions, there was an increase in active MT1-MMP but a decrease in MMP-2 protein expression. Plating cells on fibronectin protected against ischemia-induced loss of cadherins and, interestingly, no increase in active MT1-MMP levels was seen in ischemic cells on fibronectin-coated dishes. In addition, L cells stably expressing E- (LE) or N-cadherin (LN), but lacking MT1-MMP expression, were resistant to ischemia-induced cadherin loss. The role of MT1-MMP in ischemia-induced cadherin loss was confirmed by either blocking MT1-MMP activity with a neutralizing antibody or expression with shRNA constructs which protected full-length E- and N-cadherin during ischemia. Using shRNA constructs to suppress MT1-MMP expression, ischemia-induced disruption of cadherin function was ablated, and cell-cell contacts were preserved. These results demonstrate that ischemia induces increased expression of active MT1-MMP and subsequent disruption of cadherin/catenin complexes, implying that MT1-MMP plays a role in ischemia-induced ARF.
This article has been cited by other articles:
|
|
 |
|
  A. Bedel, A. Negre-Salvayre, S. Heeneman, M.-H. Grazide, J.-C. Thiers, R. Salvayre, and F. Maupas-Schwalm E-Cadherin/{beta}-Catenin/T-Cell Factor Pathway Is Involved in Smooth Muscle Cell Proliferation Elicited by Oxidized Low-Density Lipoprotein Circ. Res., September 26, 2008; 103(7): 694 - 701. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. D. Cowden Dahl, J. Symowicz, Y. Ning, E. Gutierrez, D. A. Fishman, B. P. Adley, M. S. Stack, and L. G. Hudson Matrix Metalloproteinase 9 Is a Mediator of Epidermal Growth Factor-Dependent E-Cadherin Loss in Ovarian Carcinoma Cells Cancer Res., June 15, 2008; 68(12): 4606 - 4613. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Navaratna, P. G. McGuire, G. Menicucci, and A. Das Proteolytic Degradation of VE-Cadherin Alters the Blood-Retinal Barrier in Diabetes Diabetes, September 1, 2007; 56(9): 2380 - 2387. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Taniwaki, H. Fukamachi, K. Komori, Y. Ohtake, T. Nonaka, T. Sakamoto, T. Shiomi, Y. Okada, T. Itoh, S. Itohara, et al. Stroma-Derived Matrix Metalloproteinase (MMP)-2 Promotes Membrane Type 1-MMP-Dependent Tumor Growth in Mice Cancer Res., May 1, 2007; 67(9): 4311 - 4319. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Symowicz, B. P. Adley, K. J. Gleason, J. J. Johnson, S. Ghosh, D. A. Fishman, L. G. Hudson, and M. S. Stack Engagement of Collagen-Binding Integrins Promotes Matrix Metalloproteinase-9-Dependent E-Cadherin Ectodomain Shedding in Ovarian Carcinoma Cells Cancer Res., March 1, 2007; 67(5): 2030 - 2039. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Catania, G. Chen, and A. R. Parrish Role of matrix metalloproteinases in renal pathophysiologies Am J Physiol Renal Physiol, March 1, 2007; 292(3): F905 - F911. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
