Involvement of the serine/threonine p70S6 kinase in TGF-β1-induced ADAM12 expression in cultured human hepatic stellate cells

Pabic, Hélène Le; L’Helgoualc’h, Annie; Coutant, Alexandre; Wewer, Ulla M.; Baffet, Georges; Clément, Bruno; Théret, Nathalie

doi:10.1016/j.jhep.2005.05.025

Cited by 59 publications

(54 citation statements)

References 29 publications

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“…Previous reports have shown that treatment of human hepatic stellate cells with TGF␤1 induces expression of ADAM12 (13,24). Here, we extended the analysis of TGF␤1 effects on ADAM12 expression to other cell types.…”

Section: Resultsmentioning

confidence: 85%

“…Previous studies employing hepatic stellate cells, a mesenchymal cell type in hepatic parenchyma, have indicated that ADAM12 expression is induced by transforming growth factor ␤ (TGF␤) 2 (13,24). The TGF␤ signaling pathway is initiated when one of the family members, e.g.…”

mentioning

confidence: 99%

“…Previous study on the regulation of ADAM12 expression by TGF␤ in hepatic stellate cells used rather long (24 -72 h) stimulation times and showed that ADAM12 induction was par-* This work was supported, in whole or in part, by National Institutes of Health tially blocked by inhibitors of MAPKs, phosphoinositide 3-kinase, or p70S6 kinase (13,24). Based on these results, it was postulated that induction of ADAM12 expression by TGF␤ might be Smad-independent, but a direct role of R-Smads in the regulation of ADAM12 expression has not been tested.…”

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confidence: 99%

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The Role of SnoN in Transforming Growth Factor β1-induced Expression of Metalloprotease-Disintegrin ADAM12

Solomon

Muggy

et al. 2010

Journal of Biological Chemistry

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Increased expression of metalloprotease-disintegrin ADAM12 is a hallmark of several pathological conditions, including cancer, cardiovascular disease, and certain inflammatory diseases of the central nervous system or the muscoskeletal system. We show that transforming growth factor ␤1 (TGF␤1) is a potent inducer of ADAM12 mRNA and protein in mouse fibroblasts and in mouse and human mammary epithelial cells. Induction of ADAM12 is detected within 2 h of treatment with TGF␤1, is Smad2/Smad3-dependent, and is a result of derepression of the ADAM12, a member of the metalloprotease-disintegrin family of proteins, has been implicated in the progression of cancer, cardiovascular disease, osteoarthritis, and neurological disorders (1). The ADAM12 gene is frequently mutated in human breast cancers (2, 3), and cancer-associated mutations cause mislocalization of the ADAM12 protein in cells and alter its function (4). Missense single nuclear polymorphism in the ADAM12 gene shows strong association with osteoarthritis (5, 6). In addition to changes in its amino acid sequence, expression levels of ADAM12 are significantly increased in many pathological states. For example, ADAM12 expression levels are 20 -30-fold higher in human breast tumors than in normal mammary epithelium (7-12). ADAM12 expression is also markedly up-regulated in cancers of the liver, lung, stomach, colon, prostate, bladder, and in glioblastoma (13-18). Increased ADAM12 expression levels are found in the cardiac tissue of patients with hypertrophic obstructive cardiomyopathy (19) and in mice with angiotensin II-induced hypertension and cardiac hypertrophy (20,21). During inflammatory responses and aseptic osteolysis associated with loosened hip replacement implants, ADAM12 is up-regulated in the interface tissue around loosening implants (22). In experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, ADAM12 level is markedly increased in the T cells that infiltrate spinal cords (23).The mechanisms regulating ADAM12 expression, in particular those that may be responsible for altered levels of ADAM12 in various pathological states, are poorly understood. Previous studies employing hepatic stellate cells, a mesenchymal cell type in hepatic parenchyma, have indicated that ADAM12 expression is induced by transforming growth factor ␤ (TGF␤) 2 (13, 24). The TGF␤ signaling pathway is initiated when one of the family members, e.g. TGF␤1, -␤2, or -␤3, binds to a complex of TGF␤ type I and type II serine/threonine kinase receptors (T␤RI and T␤RII, respectively) and induces phosphorylation and activation of T␤RI by T␤RII. T␤RI then phosphorylates receptor Smads (R-Smads), Smad2 and Smad3. Phosphorylated Smad2/3 associate with the common partner Smad4 and translocate to the nucleus, where they regulate transcription of target genes (25,26). In addition, receptor activation in certain cell types leads to Smad-independent responses via the activation of mitogen-activated protein kinases (MAPKs), phosphoinositide 3-kinase, and Rho family memb...

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Section: Resultsmentioning

confidence: 85%

mentioning

confidence: 99%

mentioning

confidence: 99%

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The Role of SnoN in Transforming Growth Factor β1-induced Expression of Metalloprotease-Disintegrin ADAM12

Solomon

Muggy

et al. 2010

Journal of Biological Chemistry

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“…A link has been established between TGF-β1 and cell proliferation since TGF-β1 induces a rapid activation of ADAM-17 leading in turn to EGFR signalling [138]. In activated hepatic stellate cells, TGF-βl induces ADAM-12 expression which might also participate in tumour progression [139]. It is worth pointing out that a recent study identified ADAM-12 as a partner of TGFβ receptor II signalling where it stabilizes the TGFβ RII protein and potentiates Smad-mediated signalling [140].…”

Section: Liver Carcinomamentioning

confidence: 99%

Emerging roles of ADAM and ADAMTS metalloproteinases in cancer

et al. 2008

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A disintegrin and metalloproteinases (ADAMs) are a recently discovered family of proteins that share the metalloproteinase domain with matrix metalloproteinases (MMPs). Among this family, structural features distinguish the membrane-anchored ADAMs and the secreted ADAMs with thrombospondin motifs referred to as ADAMTSs. By acting on a large panel of membrane-associated and extracellular substrates, they control several cell functions such as adhesion, fusion, migration and proliferation. The current review addresses the contribution of these proteinases in the positive and negative regulation of cancer progression as mainly mediated by the regulation of growth factor activities and integrin functions.

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“…These findings suggest a mechanism for ADAM-12 in cardiac fibrosis [32,33]. In addition, TGF-β can induce the expression of ADAM-12, which is mediated by TGF-β's ability to promote the degradation of SnoN, a negative regulator of TGF-β/Smad signaling [34,35].…”

Section: Roles Of Metalloproteinases In Disease Developmentmentioning

confidence: 91%

Metalloproteinases in hypertension and cardiac disease: differential expression and mutual regulation

Bosonea

Wang

Odenbach

et al. 2011

Drug Discovery Today: Disease Models

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Arterial hypertension, a condition characterized by sustained elevated blood pressure, is associated with pathological cardiac remodeling (i.e. cardiac hypertrophy and fibrosis) and is a major risk factor for cardiac failure. These processes can be triggered by excess vasoconstrictive agonists, which induce metalloproteinase-dependent shedding of growth factors to transactivate growth factor receptors and initiate disease signaling. Here, we review emerging evidence that agonistactivated metalloproteinases exhibit different expression patterns and mutual transcriptional regulation during the development of hypertension and cardiac remodeling.

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Involvement of the serine/threonine p70S6 kinase in TGF-β1-induced ADAM12 expression in cultured human hepatic stellate cells

Cited by 59 publications

References 29 publications

The Role of SnoN in Transforming Growth Factor β1-induced Expression of Metalloprotease-Disintegrin ADAM12

The Role of SnoN in Transforming Growth Factor β1-induced Expression of Metalloprotease-Disintegrin ADAM12

Emerging roles of ADAM and ADAMTS metalloproteinases in cancer

Metalloproteinases in hypertension and cardiac disease: differential expression and mutual regulation

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