Egr-1 Mediates Extracellular Matrix-driven Transcription of Membrane Type 1 Matrix Metalloproteinase in Endothelium

Haas, Tara L.; Stitelman, David H.; Davis, Sandra; Apte, Suneel S.; Madri, Joseph A.

doi:10.1074/jbc.274.32.22679

Cited by 169 publications

(142 citation statements)

References 34 publications

Supporting

Mentioning

139

Contrasting

Order By: Relevance

“…It has been reported that mechanical injury induces the activation of ERK, which transmits signals from the cytosol to the nucleus. Potential nucleus targets of ERK include the transcription factors ELK-1, Egr-1 and c-Fos, which are known to regulate cellular growth, differentiation, and migration [35][36][37][38]. Here we found that treatment of SMCs with berberine reduced the levels of phosphorylated ERK stimulated by injury, in the same concentration range that inhibited DNA synthesis and regrowth.…”

Section: Discussionmentioning

confidence: 60%

Berberine suppresses MEK/ERK-dependent Egr-1 signaling pathway and inhibits vascular smooth muscle cell regrowth after in vitro mechanical injury

Liang

Ting

Yin

et al. 2006

Biochemical Pharmacology

View full text Add to dashboard Cite

Vascular smooth muscle cell (SMC) proliferation plays an important role in the pathogenesis of atherosclerosis and post-angioplasty restenosis. Berberine is a well-known component of the Chinese herb medicine Huanglian (Coptis chinensis), and is capable of inhibiting SMC contraction and proliferation, yet the exact mechanism is unknown. We therefore investigated the effect of berberine on SMC growth after mechanic injury in vitro. DNA synthesis and cell proliferation assay were performed to show that berberine inhibited serum-stimulated rat aortic SMC growth in a concentration-dependent manner. Mechanical injury with sterile pipette tip stimulated the regrowth of SMCs. Treatment with berberine prevented the regrowth and migration of SMCs into the denuded trauma zone. Western blot analysis showed that activation of the MEK1/2 (mitogen-activated protein kinase kinase 1/2), extracellular signal-regulated kinase (ERK), and up-regulation of early growth response gene (Egr-1), c-Fos and Cyclin D1 were observed sequentially after mechanic injury in vitro. Semi-quantitative reverse-transcription PCR assay further confirmed the increase of Egr-1, cFos, platelet-derived growth factor (PDGF) and Cyclin D1 expression in a transcriptional level. However, berberine significantly attenuated MEK/ERK activation and downstream target (Egr-1, cFos, Cyclin D1 and PDGF-A) expression after mechanic injury in vitro. Our study showed that berberine blocked injury-induced SMC regrowth by inactivation of ERK/Egr-1 signaling pathway thereby preventing early signaling induced by injury in vitro. The anti-proliferative properties of berberine may be useful in treating disorders due to inappropriate SMC growth.

show abstract

Section: Discussionmentioning

confidence: 60%

Berberine suppresses MEK/ERK-dependent Egr-1 signaling pathway and inhibits vascular smooth muscle cell regrowth after in vitro mechanical injury

Liang

Ting

Yin

et al. 2006

Biochemical Pharmacology

View full text Add to dashboard Cite

show abstract

“…The activity of MMP-2 and MMP-9 of mouse lung fibroblast cells changed in an Egr-1-dependent manner when treated with cytomix. Although there are no Egr-1-binding sites reported in either MMP-2 or MMP-9 promoters, studies showed that the activation of pro-MMP-2 is well correlated with the expression of MIT-MMP (31), whose promoter has a binding site for Egr-1 (35). Our data suggest that EGR1 may serve as a potentially important molecule, which could play a key role in development of cigarette smoke-related COPD by regulating MMP activity and then affect the turnover of ECM proteins during pathogenesis of COPD.…”

Section: Discussionmentioning

confidence: 99%

“…Egr-1, a zinc finger transcription factor, has been termed an immediate-early response protein (33,34) and is potentially activated by a variety of cellular stressors. As a major transcription factor it alters gene expression of EGR1 target genes, including repair enzyme systems, angiogenic factors, cytokines (TNF-␣), apoptotic factors (Fas), cell cycle factors (p21, p53), metabolic factors, proteases (MT1-MMP) (35), and HO-1 (36).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive gene expression profiles reveal pathways related to the pathogenesis of chronic obstructive pulmonary disease

Ning

Kaminski

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

301

269

View full text Add to dashboard Cite

To better understand the molecular basis of chronic obstructive pulmonary disease (COPD), we used serial analysis of gene expression (SAGE) and microarray analysis to compare the gene expression patterns of lung tissues from COPD and control smokers. A total of 59,343 tags corresponding to 26,502 transcripts were sequenced in SAGE analyses. A total of 327 genes were differentially expressed (1.5-fold up-or down-regulated). Microarray analysis using the same RNA source detected 261 transcripts that were differentially expressed to a significant degree between GOLD-2 and GOLD-0 smokers. We confirmed the altered expression of a select number of genes by using real-time quantitative RT-PCR. These genes encode for transcription factors (EGR1 and FOS), growth factors or related proteins (CTGF, CYR61, CX3CL1, TGFB1, and PDGFRA), and extracellular matrix protein (COL1A1). Immunofluorescence studies on the same lung specimens localized the expression of Egr-1, CTGF, and Cyr61 to alveolar epithelial cells, airway epithelial cells, and stromal and inflammatory cells of GOLD-2 smokers. Cigarette smoke extract induced Egr-1 protein expression and increased Egr-1 DNA-binding activity in human lung fibroblast cells. Cytomix (tumor necrosis factor ␣, IL-1␤, and IFN-␥) treatment showed that the activity of matrix metalloproteinase-2 (MMP-2) was increased in lung fibroblasts from EGR1 control (؉/؉) mice but not detected in that of EGR1 null (؊/؊) mice, whereas MMP-9 was regulated by EGR1 in a reverse manner. Our study represents the first comprehensive analysis of gene expression on GOLD-2 versus GOLD-0 smokers and reveals previously unreported candidate genes that may serve as potential molecular targets in COPD.

show abstract

“…The promoter region of MT1-MMP has many putative transcription factor binding sites (30), several of which have been demonstrated to regulate MT1-MMP expression (31-34). Among those, EGR1 was shown to play a role in induction of MT1-MMP in murine endothelial cells in collagen culture (31). In addition to EGR1, several related transcription factors including EGR2, -3, and -4, and SP1 share a similar consensus sequence (35)(36)(37)(38).…”

Section: Mt1-mmp Induction In Three-dimensional Collagen I Is Transcrmentioning

confidence: 99%

Microenvironmental Regulation of Membrane Type 1 Matrix Metalloproteinase Activity in Ovarian Carcinoma Cells via Collagen-induced EGR1 Expression

Barbolina

Adley

Ariztia

et al. 2007

Journal of Biological Chemistry

122

View full text Add to dashboard Cite

Late stage ovarian cancer is characterized by disseminated intraperitoneal metastasis as secondary lesions anchor in the type I and III collagen-rich submesothelial matrix. Ovarian carcinoma cells preferentially adhere to interstitial collagen, and collagen-induced integrin clustering up-regulates the expression of the transmembrane collagenase membrane type 1 matrix metalloproteinase (MT1-MMP). Collagenolytic activity is important in intraperitoneal metastasis, potentiating invasion through the mesothelial cell layer and colonization of the submesothelial collagen-rich matrix. The objective of this study was to elucidate a potential mechanistic link between collagen adhesion and MT1-MMP expression. Our results indicate that culturing cells on three-dimensional collagen gels, but not thin layer collagen or synthetic threedimensional hydrogels, results in rapid induction of the transcription factor EGR1. Integrin signaling through a SRC kinasedependent pathway is necessary for EGR1 induction. Silencing of EGR1 expression using small interfering RNA abrogated collagen-induced MT1-MMP expression and inhibited cellular invasion of three-dimensional collagen gels. These data support a model for intraperitoneal metastasis wherein collagen adhesion and clustering of collagen binding integrins activates integrin-mediated signaling via SRC kinases to induce expression of EGR1, resulting in transcriptional activation of the MT1-MMP promoter and subsequent MT1-MMP-catalyzed collagen invasion. This model highlights the role of unique interactions between ovarian carcinoma cells and interstitial collagens in the ovarian tumor microenvironment in inducing gene expression changes that potentiate intraperitoneal metastatic progression.Epithelial ovarian carcinoma is the leading cause of death from gynecologic malignancy (1), due primarily to the fact that the majority of patients are diagnosed at late stage (III and IV) when metastasis has already occurred. Approximately 10% of all epithelial ovarian carcinomas are hereditary and may be facilitated by gene mutations, whereas the remaining 90% are sporadic (2-6). Tumors are thought to arise from the single cell layer of the ovarian epithelium and metastasis occurs via direct extension into the peritoneal cavity, where shed cells from the primary tumor are found as a component of malignant ascites. Secondary tumors arise as a consequence of CD44-and integrin-mediated intra-peritoneal adhesion and localized invasion into the interstitial collagen-rich submesothelial matrix. Proteolytic activity is important at multiple stages in intraperitoneal metastasis, including disruption of cell-cell interactions, migration and invasion into the mesothelial cell layer, and the submesothelial matrix to anchor secondary lesions, and for subsequent tumor-mediated angiogenesis (7).Multiple studies have shown that microenvironmental contacts with stromal cells or extracellular matrix elements may play a major role in tumor progression by inducing epigenetic changes in transformed cells (8,9). Met...

show abstract

Egr-1 Mediates Extracellular Matrix-driven Transcription of Membrane Type 1 Matrix Metalloproteinase in Endothelium

Cited by 169 publications

References 34 publications

Berberine suppresses MEK/ERK-dependent Egr-1 signaling pathway and inhibits vascular smooth muscle cell regrowth after in vitro mechanical injury

Berberine suppresses MEK/ERK-dependent Egr-1 signaling pathway and inhibits vascular smooth muscle cell regrowth after in vitro mechanical injury

Comprehensive gene expression profiles reveal pathways related to the pathogenesis of chronic obstructive pulmonary disease

Microenvironmental Regulation of Membrane Type 1 Matrix Metalloproteinase Activity in Ovarian Carcinoma Cells via Collagen-induced EGR1 Expression

Contact Info

Product

Resources

About