Signal transduction and cell‐type specific regulation of matrix metalloproteinase gene expression: Can MMPs be good for you?

Vincenti, Matthew P.; Brinckerhoff, Constance E.

doi:10.1002/jcp.21208

Cited by 159 publications

(157 citation statements)

References 90 publications

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“…Further studies are required to define the exact molecular source of ROS generation upon TNF-α stimulation. Although the signaling pathways for expression of MMP-9 are complex (22), previous studies demonstrated that TNF-α induces up-regulation of MMP-9 expression and release via an NF-κB-dependent pathway in keratinocytes (7,8). We performed experiments to analyze the effect of Tat-SOD on activation of NF-κB in TNF-α-stimulated HaCaT cells.…”

Section: Discussionmentioning

confidence: 99%

Suppression of TNF-alpha-induced MMP-9 expression by a cell-permeable superoxide dismutase in keratinocytes

Song

Ju²,

Goh³

et al. 2011

BMB Reports

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Section: Discussionmentioning

confidence: 99%

Suppression of TNF-alpha-induced MMP-9 expression by a cell-permeable superoxide dismutase in keratinocytes

Song

Ju²,

Goh³

et al. 2011

BMB Reports

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“…IL-1β activation of MMP-1 transcription requires the input of multiple signaling pathways with the nuclear factor-κB (NF-κB) transcription factors and mitogen-activated protein kinases playing dominant roles (1). Our studies have shown that RelA is required for IL-1β induction of MMP-1, whereas NF-κB1 and NF-κB2 act as inhibitors of gene expression (10).…”

Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

“…In disease states such as arthritis and cancer, MMP expression is inappropriately activated, causing pathologic connective tissue destruction and cellular invasion (1). Among the 23 identified human MMP family members (2), MMP-1 (collagenase-1) is broadly expressed by mesenchymal and epithelial cells and degrades interstitial collagens, the most abundant extracellular matrix proteins in the body (1). It has long been appreciated that inflammation-dependent activation of MMP-1 gene expression in synovial cells and chondrocytes contributes to joint destruction in rheumatoid arthritis and osteoarthritis (3).…”

Section: Introductionmentioning

confidence: 99%

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CCAAT Enhancer Binding Protein-β Regulates Matrix Metalloproteinase-1 Expression in Interleukin-1β–Stimulated A549 Lung Carcinoma Cells

Armstrong¹,

Phelps²,

Vincenti³

2009

Molecular Cancer Research

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Matrix metalloproteinase-1 (MMP-1) is an inflammationinducible neutral protease that mediates extracellular matrix remodeling and promotes tumor invasion. In this study, we examined the activation of MMP-1 gene expression in A549 lung carcinoma cells stimulated with the inflammatory cytokine interleukin-1β (IL-1β). We found that MMP-1 mRNA levels were maximal following 16 hours of IL-1β stimulation and that this correlated with the expression of the transcription factor CCAAT enhancer-binding protein-β (CEBPB). Knockdown of CEBPB expression with short hairpin RNA abrogated the expression of MMP-1, MMP-3, and MMP-10 in IL-1β-stimulated A549 cells. An established CEBP element in the MMP-1 promoter was found to be required for basal and IL-1β-induced transcription. Electrophoresis mobility shift assays showed that CEBPB binds to this promoter element maximally 16 hours after IL-1β stimulation. DNA affinity chromatography studies showed that the LAP1, LAP2, and LIP isoforms of CEBPB bind to the IL-1β-responsive CEBPB site in the MMP-1 promoter. Exogenous expression of the LAP1 and LAP2 isoforms stimulated the MMP-1 promoter, whereas LIP had no effect. Phosphorylation of CEBPB at Thr 235 peaked at 16 hours in IL-1β-stimulated cells. The MEK inhibitor U0126 inhibited this phosphorylation and reduced MMP-1 gene induction. These studies establish CEBPB as an important mediator of metalloproteinase gene activation during inflammatory responses in lung cancer cells and highlight the different regulatory roles of CEBPB isoforms. (Mol Cancer Res 2009;7(9):1517-24)

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“…The promoter regions of MMPs and TIMPs contain activator protein 1 and Ets binding sites and are activated by EGF (22,36,41,58). Ets-1 is one of the mediators of ECM remodeling associated with the regulation of MMPs and hence connected to ECM degradation (43).…”

Section: Discussionmentioning

confidence: 99%

Blockade of Ets-1 attenuates epidermal growth factor-dependent collagen loss in human carotid plaque smooth muscle cells

Rao

Rai

Stoupa

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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Rao VH, Rai V, Stoupa S, Agrawal DK. Blockade of Ets-1 attenuates epidermal growth factor-dependent collagen loss in human carotid plaque smooth muscle cells. Am J Physiol Heart Circ Physiol 309: H1075-H1086, 2015. First published August 7, 2015 doi:10.1152/ajpheart.00378.2015.-Although degradation of extracellular matrix by matrix metalloproteinases (MMPs) is thought to be involved in symptomatic (S) carotid plaques in atherosclerosis, the mechanisms of MMP expression are poorly understood. Here, we demonstrate that collagen loss in vascular smooth vessel cells (VSMCs) isolated from S plaques was induced by epidermal growth factor (EGF) through the activation of p38-MAPK and JNK-MAPK pathways. Inhibitors of p38-MAPK and JNK-MAPK signaling pathways downregulated the expression of MMP-1 and MMP-9. In addition, we examined whether v-ets erythroblastosis virus E26 oncogene homologue 1 (Ets-1), an important regulator of different genes, is involved in destabilizing S plaques in patients with carotid stenosis. We demonstrate that EGF induces Ets-1 expression and decreases interstitial and basement membrane collagen in vascular smooth muscle cells (VSMCs) from patients with carotid stenosis. Increased expression of MMP-1 and -9 and decreased collagen mRNA transcripts were also found in Ets-1-overexpressed VSMCs. Transfection with both dominant-negative form of Ets-1 and small interfering RNA blocked EGF-induced MMP-1 and -9 expressions and increased the mRNA transcripts for collagen I (␣ 1) and collagen III (␣1) in S compared with asymptomatic (AS) carotid plaques. Inhibitors of p38-MAPK (SB202190) and JNK-MAPK (SP600125) signaling pathways decreased the expression of Ets-1, MMP-1, and MMP-9 and increased collagen type I and III expression in EGF-treated VSMCs. This study provides a mechanistic insight into the role of Ets-1 in the plaque destabilization in patients with carotid stenosis involving p38-MAPK and JNK signaling pathways. carotid plaque; collagen types I and III; epidermal growth factor; matrix metalloproteinases; v-ets erythroblastosis virus E26 oncogene homologue 1; vascular smooth muscle cells NEW & NOTEWORTHY This study provides a mechanistic insight into the role of Ets-1 regulated EGF induced collagen loss involving p38-MAPK and JNK signaling pathways in human carotid plaques with carotid stenosis. Selective blockade of Ets-1 and EGF receptor may be a novel strategy and promising target for treating unstable and vulnerable plaques.ATHEROSCLEROSIS IS A COMPLEX disease with coronary thrombus leading to stroke and is the major cause of morbidity and mortality throughout the world (8, 24). The matrix accumulation and degradation in the extracellular matrix (ECM) may determine the outcome of plaque stability (1). Proteases produced by the cellular components of the plaque are thought to be mainly responsible for thinning of the plaque cap and the development of myocardial infarction and stroke. Inflammatory cytokines (tumor necrosis factor-␣ and interleukin-1) and growth factors [epidermal growth factor ...

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Signal transduction and cell‐type specific regulation of matrix metalloproteinase gene expression: Can MMPs be good for you?

Cited by 159 publications

References 90 publications

Suppression of TNF-alpha-induced MMP-9 expression by a cell-permeable superoxide dismutase in keratinocytes

Suppression of TNF-alpha-induced MMP-9 expression by a cell-permeable superoxide dismutase in keratinocytes

CCAAT Enhancer Binding Protein-β Regulates Matrix Metalloproteinase-1 Expression in Interleukin-1β–Stimulated A549 Lung Carcinoma Cells

Blockade of Ets-1 attenuates epidermal growth factor-dependent collagen loss in human carotid plaque smooth muscle cells

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