help button home button Am J Pathol Epitomics Buy 2 Antibodies Get 1 Free Special Offer
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 Ferri, N.
Right arrow Articles by Raines, E. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ferri, N.
Right arrow Articles by Raines, E. W.
(American Journal of Pathology. 2004;164:1575-1585.)
© 2004 American Society for Investigative Pathology

Role of Discoidin Domain Receptors 1 and 2 in Human Smooth Muscle Cell-Mediated Collagen Remodeling

Potential Implications in Atherosclerosis and Lymphangioleiomyomatosis

Nicola Ferri, Neil O. Carragher and Elaine W. Raines

From the Department of Pathology, University of Washington School of Medicine, Seattle, Washington

Obstructive diseases of blood vessels and the lung are characterized by degradation and synthesis of new extracellular matrix (ECM) components. Regulated remodeling of the ECM in diseases such as atherosclerosis and lymphangioleiomyomatosis (LAM), both characterized by excessive accumulation of smooth muscle cells (SMCs), is thought to be controlled in part by cell surface receptors for specific ECM components. Discoidin domain receptors (DDR) 1 and 2 represent a family of tyrosine kinase collagen receptors that are activated by fibrillar collagens. To test the hypothesis that DDR may be involved in ECM remodeling by SMCs in vivo, we analyzed DDR expression by reverse transcriptase-polymerase chain reaction and immunohistochemistry and demonstrate that both DDR1 and DDR2 are up-regulated in nodules of LAM as compared to normal controls, and are expressed in lesions of atherosclerosis. In vitro, retroviral overexpression of DDR1 or DDR2 in human SMCs cultured on polymerized collagen gels leads to a reduction of collagen expression and induces matrix metalloproteinase (MMP) 1 at both mRNA and protein levels, but only DDR2 enhances MMP2 activation. Moreover, DDR2 overexpression increases SMC-mediated collagen and elastin degradation in vitro. Using laser microdissection, we extend our studies to the analysis of SMCs from LAM nodules where we observe higher MMP1 expression and MMP2 activation. Taken together, these data provide evidence for the potential roles of DDR1 and DDR2 in the regulation of collagen turnover mediated by SMCs in obstructive diseases of blood vessels and the lung.




This article has been cited by other articles:


Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
K.-G. Shyu, B.-W. Wang, P. Kuan, and H. Chang
RNA Interference for Discoidin Domain Receptor 2 Attenuates Neointimal Formation in Balloon Injured Rat Carotid Artery
Arterioscler. Thromb. Vasc. Biol., August 1, 2008; 28(8): 1447 - 1453.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
C. Franco, G. Hou, P. J. Ahmad, E. Y.K. Fu, L. Koh, W. F. Vogel, and M. P. Bendeck
Discoidin Domain Receptor 1 (Ddr1) Deletion Decreases Atherosclerosis by Accelerating Matrix Accumulation and Reducing Inflammation in Low-Density Lipoprotein Receptor-Deficient Mice
Circ. Res., May 23, 2008; 102(10): 1202 - 1211.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. Abdulhussein, D. H. H. Koo, and W. F. Vogel
Identification of Disulfide-linked Dimers of the Receptor Tyrosine Kinase DDR1
J. Biol. Chem., May 2, 2008; 283(18): 12026 - 12033.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. D. Konitsiotis, N. Raynal, D. Bihan, E. Hohenester, R. W. Farndale, and B. Leitinger
Characterization of High Affinity Binding Motifs for the Discoidin Domain Receptor DDR2 in Collagen
J. Biol. Chem., March 14, 2008; 283(11): 6861 - 6868.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
G. Pacheco-Rodriguez, W. K. Steagall, D. M. Crooks, L. A. Stevens, H. Hashimoto, S. Li, J.-a. Wang, T. N. Darling, and J. Moss
TSC2 Loss in Lymphangioleiomyomatosis Cells Correlated with Expression of CD44v6, a Molecular Determinant of Metastasis
Cancer Res., November 1, 2007; 67(21): 10573 - 10581.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. GenomicsHome page
G. Rajashekhar, M. Grow, A. Willuweit, C. E. Patterson, and M. Clauss
Divergent and convergent effects on gene expression and function in acute versus chronic endothelial activation
Physiol Genomics, September 11, 2007; 31(1): 104 - 113.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
N. Ferri, G. Colombo, C. Ferrandi, E. W. Raines, B. Levkau, and A. Corsini
Simvastatin Reduces MMP1 Expression in Human Smooth Muscle Cells Cultured on Polymerized Collagen by Inhibiting Rac1 Activation
Arterioscler. Thromb. Vasc. Biol., May 1, 2007; 27(5): 1043 - 1049.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
C. Avivi-Green, M. Singal, and W. F. Vogel
Discoidin Domain Receptor 1-deficient Mice Are Resistant to Bleomycin-induced Lung Fibrosis
Am. J. Respir. Crit. Care Med., August 15, 2006; 174(4): 420 - 427.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
N. A. Noordeen, F. Carafoli, E. Hohenester, M. A. Horton, and B. Leitinger
A Transmembrane Leucine Zipper Is Required for Activation of the Dimeric Receptor Tyrosine Kinase DDR1
J. Biol. Chem., August 11, 2006; 281(32): 22744 - 22751.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
E. A. Goncharova, D. A. Goncharov, P. N. Lim, D. Noonan, and V. P. Krymskaya
Modulation of Cell Migration and Invasiveness by Tumor Suppressor TSC2 in Lymphangioleiomyomatosis
Am. J. Respir. Cell Mol. Biol., April 1, 2006; 34(4): 473 - 480.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
A. C. Newby
Matrix metalloproteinases regulate migration, proliferation, and death of vascular smooth muscle cells by degrading matrix and non-matrix substrates
Cardiovasc Res, February 15, 2006; 69(3): 614 - 624.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
W. Matsuyama, M. Watanabe, Y. Shirahama, R. Hirano, H. Mitsuyama, I. Higashimoto, M. Osame, and K. Arimura
Suppression of Discoidin Domain Receptor 1 by RNA Interference Attenuates Lung Inflammation
J. Immunol., February 1, 2006; 176(3): 1928 - 1936.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. J. Wall, E. Werner, Z. Werb, and Y. A. DeClerck
Discoidin Domain Receptor 2 Mediates Tumor Cell Cycle Arrest Induced by Fibrillar Collagen
J. Biol. Chem., December 2, 2005; 280(48): 40187 - 40194.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Yang, J. H. Kim, H. J. Kim, I.-S. Park, I. Y. Kim, and B.-S. Yang
Tyrosine 740 Phosphorylation of Discoidin Domain Receptor 2 by Src Stimulates Intramolecular Autophosphorylation and Shc Signaling Complex Formation
J. Biol. Chem., November 25, 2005; 280(47): 39058 - 39066.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
K.-G. Shyu, Y.-M. Chao, B.-W. Wang, and P. Kuan
Regulation of Discoidin Domain Receptor 2 by Cyclic Mechanical Stretch in Cultured Rat Vascular Smooth Muscle Cells
Hypertension, September 1, 2005; 46(3): 614 - 621.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
C. Renne, K. Willenbrock, R. Kuppers, M.-L. Hansmann, and A. Brauninger
Autocrine- and paracrine-activated receptor tyrosine kinases in classic Hodgkin lymphoma
Blood, May 15, 2005; 105(10): 4051 - 4059.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2004 by the American Society for Investigative Pathology.