help button home button Am J Pathol sign up for etoc
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zeisberg, M.
Right arrow Articles by Kalluri, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zeisberg, M.
Right arrow Articles by Kalluri, R.
(American Journal of Pathology. 2002;160:2001-2008.)
© 2002 American Society for Investigative Pathology

Regular Articles

Renal Fibrosis

Extracellular Matrix Microenvironment Regulates Migratory Behavior of Activated Tubular Epithelial Cells

Michael Zeisberg, Yohei Maeshima, Barbara Mosterman and Raghu Kalluri

From the Department of Medicine and the Liver Center, Program in Matrix Biology, Renal, and Gastroenterology Divisions, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts

During progression of chronic renal disease, qualitative and quantitative changes in the composition of tubular basement membranes (TBMs) and interstitial matrix occur. Transforming growth factor (TGF)-ß1-mediated activation of tubular epithelial cells (TECs) is speculated to be a key contributor to the progression of tubulointerstitial fibrosis. To further understand the pathogenesis associated with renal fibrosis, we developed an in vitro Boyden chamber system using renal basement membranes that partially mimics in vivo conditions of TECs during health and disease. Direct stimulation of TECs with TGF-ß1/epithelial growth factor results in an increased migratory capacity across bovine TBM preparations. This is associated with increased matrix metalloproteinase (MMP) production, namely MMP-2 and MMP-9. Indirect chemotactic stimulation by TGF-ß1/EGF or collagen type I was insufficient in inducing migration of untreated TECs across bovine TBM preparation, suggesting that basement membrane integrity and composition play an important role in protecting TECs from interstitial fibrotic stimuli. Additionally, neutralization of MMPs by COL-3 inhibitor dramatically decreases the capacity of TGF-ß1-stimulated TECs to migrate through bovine TBM preparation. Collectively, these results demonstrate that basement membrane structure, integrity, and composition play an important role in determining interstitial influences on TECs and subsequent impact on potential aberrant cell-matrix interactions.




This article has been cited by other articles:


Home page
 J. Cell Biol.Home page
Y. Shintani, Y. Fukumoto, N. Chaika, R. Svoboda, M. J. Wheelock, and K. R. Johnson
Collagen I-mediated up-regulation of N-cadherin requires cooperative signals from integrins and discoidin domain receptor 1
J. Cell Biol., March 24, 2008; 180(6): 1277 - 1289.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Zeisberg, C. Yang, M. Martino, M. B. Duncan, F. Rieder, H. Tanjore, and R. Kalluri
Fibroblasts Derive from Hepatocytes in Liver Fibrosis via Epithelial to Mesenchymal Transition
J. Biol. Chem., August 10, 2007; 282(32): 23337 - 23347.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
L. R. White, J. B. Blanchette, L. Ren, A. Awn, K. Trpkov, and D. A. Muruve
The characterization of {alpha}5-integrin expression on tubular epithelium during renal injury
Am J Physiol Renal Physiol, February 1, 2007; 292(2): F567 - F576.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
F. Strutz and G. A. Muller
Renal fibrosis and the origin of the renal fibroblast
Nephrol. Dial. Transplant., December 1, 2006; 21(12): 3368 - 3370.
[Full Text] [PDF]

Home page
 Cancer Res.Home page
J. R.E. Rees, B. A. Onwuegbusi, V. E. Save, D. Alderson, and R. C. Fitzgerald
In vivo and In vitro Evidence for Transforming Growth Factor-{beta}1-Mediated Epithelial to Mesenchymal Transition in Esophageal Adenocarcinoma
Cancer Res., October 1, 2006; 66(19): 9583 - 9590.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
S. Cheng, A. S. Pollock, R. Mahimkar, J. L. Olson, and D. H. Lovett
Matrix metalloproteinase 2 and basement membrane integrity: a unifying mechanism for progressive renal injury
FASEB J, September 1, 2006; 20(11): 1898 - 1900.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
S. Yamashita, A. Maeshima, and Y. Nojima
Involvement of Renal Progenitor Tubular Cells in Epithelial-to-Mesenchymal Transition in Fibrotic Rat Kidneys
J. Am. Soc. Nephrol., July 1, 2005; 16(7): 2044 - 2051.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
M. A. Gratton, V. H. Rao, D. T. Meehan, C. Askew, and D. Cosgrove
Matrix Metalloproteinase Dysregulation in the Stria Vascularis of Mice with Alport Syndrome: Implications for Capillary Basement Membrane Pathology
Am. J. Pathol., May 1, 2005; 166(5): 1465 - 1474.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Zeisberg, A. A. Shah, and R. Kalluri
Bone Morphogenic Protein-7 Induces Mesenchymal to Epithelial Transition in Adult Renal Fibroblasts and Facilitates Regeneration of Injured Kidney
J. Biol. Chem., March 4, 2005; 280(9): 8094 - 8100.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
A. A. Eddy
Proteinuria and interstitial injury
Nephrol. Dial. Transplant., February 1, 2004; 19(2): 277 - 281.
[Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
H. Robertson, S. Ali, B. J. McDonnell, A. D. Burt, and J. A. Kirby
Chronic Renal Allograft Dysfunction: The Role of T Cell-Mediated Tubular Epithelial to Mesenchymal Cell Transition
J. Am. Soc. Nephrol., February 1, 2004; 15(2): 390 - 397.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C. Yang, M. Zeisberg, J. C. Lively, P. Nyberg, N. Afdhal, and R. Kalluri
Integrin {alpha}1{beta}1 and {alpha}2{beta}1 Are the Key Regulators of Hepatocarcinoma Cell Invasion Across the Fibrotic Matrix Microenvironment
Cancer Res., December 1, 2003; 63(23): 8312 - 8317.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
M. Zeisberg, C. Bottiglio, N. Kumar, Y. Maeshima, F. Strutz, G. A. Muller, and R. Kalluri
Bone morphogenic protein-7 inhibits progression of chronic renal fibrosis associated with two genetic mouse models
Am J Physiol Renal Physiol, December 1, 2003; 285(6): F1060 - F1067.
[Abstract] [Full Text]

Home page
 NEJMHome page
B. G. Hudson, K. Tryggvason, M. Sundaramoorthy, and E. G. Neilson
Alport's Syndrome, Goodpasture's Syndrome, and Type IV Collagen
N. Engl. J. Med., June 19, 2003; 348(25): 2543 - 2556.
[Full Text] [PDF]

Home page
 Cancer Res.Home page
C. Xue, D. Plieth, C. Venkov, C. Xu, and E. G. Neilson
The Gatekeeper Effect of Epithelial-Mesenchymal Transition Regulates the Frequency of Breast Cancer Metastasis
Cancer Res., June 15, 2003; 63(12): 3386 - 3394.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
J.-J. Boffa, Y. Lu, S. Placier, A. Stefanski, J.-C. Dussaule, and C. Chatziantoniou
Regression of Renal Vascular and Glomerular Fibrosis: Role of Angiotensin II Receptor Antagonism and Matrix Metalloproteinases
J. Am. Soc. Nephrol., May 1, 2003; 14(5): 1132 - 1144.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
Y.-C. Tian and A. O. Phillips
TGF-{beta}1-Mediated Inhibition of HK-2 Cell Migration
J. Am. Soc. Nephrol., March 1, 2003; 14(3): 631 - 640.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2002 by the American Society for Investigative Pathology.