Collagen binding α2β1 and α1β1 integrins play contrasting roles in regulation of Ets-1 expression in human liver myofibroblasts

Znoyko, Iya; Trojanowska, Maria; Reuben, Adrian

doi:10.1007/s11010-006-1400-0

Cited by 24 publications

(20 citation statements)

References 53 publications

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“…They are heterodimeric transmembrane proteins composed of ␣-and ␤-subunits whose ligands are matrix molecules rather than cytokines. Several integrins, disintegrins, related molecules, and their downstream effectors have been identified in stellate cells, including ␣1␤1, ␣2␤1, ␣6␤4, ␣8␤1, ␣v␤1, and ␣v␤3, and integrinlinked kinase (92,140,178,185,220,269,302,339,347,392,408,447,494,508,509,593,694,735,736,738). In particular, integrin ligands contain an arginine (Arg)-glycine (Gly)-aspartate (Asp) tripeptide sequence.…”

Section: Biology Of Membrane Receptorsmentioning

confidence: 99%

Hepatic Stellate Cells: Protean, Multifunctional, and Enigmatic Cells of the Liver

Friedman

2008

Physiological Reviews

2,419

2,549

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The hepatic stellate cell has surprised and engaged physiologists, pathologists, and hepatologists for over 130 years, yet clear evidence of its role in hepatic injury and fibrosis only emerged following the refinement of methods for its isolation and characterization. The paradigm in liver injury of activation of quiescent vitamin A-rich stellate cells into proliferative, contractile, and fibrogenic myofibroblasts has launched an era of astonishing progress in understanding the mechanistic basis of hepatic fibrosis progression and regression. But this simple paradigm has now yielded to a remarkably broad appreciation of the cell's functions not only in liver injury, but also in hepatic development, regeneration, xenobiotic responses, intermediary metabolism, and immunoregulation. Among the most exciting prospects is that stellate cells are essential for hepatic progenitor cell amplification and differentiation. Equally intriguing is the remarkable plasticity of stellate cells, not only in their variable intermediate filament phenotype, but also in their functions. Stellate cells can be viewed as the nexus in a complex sinusoidal milieu that requires tightly regulated autocrine and paracrine cross-talk, rapid responses to evolving extracellular matrix content, and exquisite responsiveness to the metabolic needs imposed by liver growth and repair. Moreover, roles vital to systemic homeostasis include their storage and mobilization of retinoids, their emerging capacity for antigen presentation and induction of tolerance, as well as their emerging relationship to bone marrow-derived cells. As interest in this cell type intensifies, more surprises and mysteries are sure to unfold that will ultimately benefit our understanding of liver physiology and the diagnosis and treatment of liver disease.

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Section: Biology Of Membrane Receptorsmentioning

confidence: 99%

Hepatic Stellate Cells: Protean, Multifunctional, and Enigmatic Cells of the Liver

Friedman

2008

Physiological Reviews

2,419

2,549

View full text Add to dashboard Cite

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“…Changes in MMP expression are paralleled by changed expression of Ets-1 transcription factor. 103,121 The induction of MMP-13 in periodontal ligament fibroblasts is dependent on integrin a11b1. 122 The induction of MMP in collagen gel may be affected by signaling pathways downstream of integrin ligand binding.…”

mentioning

confidence: 99%

Collagen matrix as a tool in studying fibroblastic cell behavior

Kanta

2015

Cell Adhesion & Migration

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“…Several ECM genes, including type I colla- gen, are regulated by Ets-1 (61). It has been shown that elevated expression of recombinant Ets-1 has the potential to suppress the transcription of type I collagen and increase matrix degradation in transforming growth factor-␤-treated cells (28,31,47).…”

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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Collagen binding α2β1 and α1β1 integrins play contrasting roles in regulation of Ets-1 expression in human liver myofibroblasts

Cited by 24 publications

References 53 publications

Hepatic Stellate Cells: Protean, Multifunctional, and Enigmatic Cells of the Liver

Hepatic Stellate Cells: Protean, Multifunctional, and Enigmatic Cells of the Liver

Collagen matrix as a tool in studying fibroblastic cell behavior

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

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