Cadmium induces matrix metalloproteinase-9 expression via ROS-dependent EGFR, NF-кB, and AP-1 pathways in human endothelial cells

Lian, Sen; Xia, Yong; Khoi, Pham Ngoc; Ung, Trong Thuan; Yoon, Hyun Joong; Kim, Nam Ho; Kim, Kyung Keun; Jung, Young Do

doi:10.1016/j.tox.2015.10.008

Cited by 66 publications

(35 citation statements)

References 44 publications

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“…In this study, inhibition of p-p38, p-ERK1/2 and p-JNK1/2 all markedly attenuated MMP-9 expression in 2-CE exposed astrocytes, suggesting that all three kinds of MAPK signal pathways were activated, and collectively involved in modulation of MMP-9 expression in 2-CE exposed astrocytes. Until now, there is a large body of evidence to suggest that MMP-9 expression is regulated by p38, ERKs and JNKs in different cell types (Lee et al, 2014; Kim et al, 2015; Lian et al, 2015). However, as far as we know, this is the first time to discuss the molecular mechanisms of MMP-9 expression regulation in astrocytes exposed to 2-CE.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of Matrix Metalloproteinase-9 in Primary Cultured Rat Astrocytes Induced by 2-Chloroethanol Via MAPK Signal Pathways

Wang

Liao

Sun

et al. 2017

Front. Cell. Neurosci.

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2-Chloroethanol (2-CE) is one of the reactive metabolites of 1,2-DCE in vivo, which might contribute to brain edema formation induced by 1,2-dichloroethane (1,2-DCE) poisoning. Thus, the purpose of this study was to explore the roles of mitogen-activated protein kinase (MAPK) signal pathways in upregulation of matrix metalloproteinase-9 (MMP-9) in 2-CE exposed rat astrocytes. Expression of p38 MAPK (p38), extracellular signal regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK) and MMP-9 at both protein and gene levels in rat astrocytes were determined using western blot and real-time RT-PCR methods. The results showed that both protein and mRNA levels of MMP-9 in 2-CE exposed astrocytes significantly increased. Meanwhile, protein levels of phosphorylated p38 (p-p38), ERK1/2 (p-ERK1/2) and JNK1/2 (p-JNK1/2) in 2-CE exposed astrocytes also significantly increased. In addition, both protein and mRNA levels of MMP-9 significantly decreased in response to reduced protein levels of p-p38, p-ERK1/2 and p-JNK1/2 achieved by supplement with their specific inhibitors, indicating that activation of MAPK signal pathways might play an important role in upregulation of MMP-9 expression at the transcriptional level in 2-CE exposed astrocytes. Furthermore, since pretreatment of n-acetyl-l-cysteine (NAC), a powerful antioxidant amino acid, could attenuate the elevated levels of MMP-9, p-p38, p-ERK2 and p-JNK1/2 in 2-CE exposed astrocytes, activation of MAPK signal pathways in 2-CE exposed astrocytes could be mediated partially by reactive oxygen species (ROS), which was most likely generated in the metabolism of 2-CE.

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Section: Discussionmentioning

confidence: 99%

Upregulation of Matrix Metalloproteinase-9 in Primary Cultured Rat Astrocytes Induced by 2-Chloroethanol Via MAPK Signal Pathways

Wang

Liao

Sun

et al. 2017

Front. Cell. Neurosci.

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“…In our study, Act.D and CHX experiments revealed that LPA-induced MMP-9 expression was up-regulated at the de novo synthesis of mRNA - transcriptional level. A variety of transcription factors for regulating MMP-9 are investigated, such as NF-κB (Dilly et al, 2013; Tseng et al, 2013; Yan et al, 2016), activator protein-1 (AP-1) (Lian et al, 2015; Yang et al, 2016), specificity protein 1 (Sp-1) (Murthy et al, 2012) and peroxisome proliferator-activated receptor-γ (PPARγ) (Lee et al, 2009; Chen et al, 2013). We showed that LPA-mediated MMP-9 expression in macrophages is dependent on NF-κB signaling through inhibitor experiments and promoter analysis.…”

Section: Discussionmentioning

confidence: 99%

Lysophosphatidic Acid Is Associated with Atherosclerotic Plaque Instability by Regulating NF-κB Dependent Matrix Metalloproteinase-9 Expression via LPA2 in Macrophages

Wang

Zhao

et al. 2017

Front. Physiol.

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Lysophosphatidic acid (LPA), one of the simplest phospholipid signaling molecules, participates in formation and disruption of atherosclerotic plaque. Matrix metalloproteinases (MMPs) contribute to atherosclerotic plaque rupture by involving in extracellular matrix (ECM) degradation and then thinning fibrous cap. Our previous study demonstrated that macrophage-derived MMP-9 was associated with coronary plaque instability, but the relationship between LPA and MMP-9 remains unclear. The present work therefore aimed at elucidating association between LPA and MMP-9 and the regulation mechanism of LPA on MMP-9 in macrophages. We found that plasma LPA and MMP-9 levels were correlated positively (r = 0.31, P < 0.05) and both elevated significantly in patients with acute myocardial infarct (AMI). Consistent with peripheral blood levels, histochemical staining indicated that autotaxin (ATX), LPA-producing ectoenzyme, and MMP-9 were expressed frequently in the necrotic core and fibrous cap of human unstable plaques, which might increase the instability of plaque. Experiments in vitro were done with THP-1-derived macrophages and showed that LPA enhanced the expression, secretion and activity of MMP-9 in a time- and dose-dependent manner. Induction of LPA on pro-MMP-9 and active-MMP-9 was confirmed in human peripheral blood monocyte-derived macrophages. PDTC, NF-κB inhibitor, but not inhibitor of AP-1 and PPARγ, effectively prevented LPA-induced MMP-9 expression and NF-κB p65 siRNA decreased MMP-9 transcription, confirming that LPA might induce MMP-9 elevation by activating NF-κB pathway. In addition, knockdown of LPA2 attenuated LPA-induced MMP-9 expression and nucleus p65 levels. These findings revealed that LPA upregulated the expression of MMP-9 through activating NF-κB pathway in the LPA2 dependent manner, hence blocking LPA receptors signaling may provide therapeutic strategy to target plaque destabilization.

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“…The MMP-9 promoter region consists of serial binding elements for interaction of transcription factors including AP-1, recognized as an inflammation-related regulator of cellular activities [31,32]. Thrombin has been shown to activate AP-1 which regulates cellular functions including induction of MMP-9 in various cell types [3,18].…”

Section: Thrombin Induces Mmp-9 Expression Via Pi3k/akt Signaling Patmentioning

confidence: 99%

Thrombin Enhanced Matrix Metalloproteinase-9 Expression and Migration of SK-N-SH Cells via PAR-1, c-Src, PYK2, EGFR, Erk1/2 and AP-1

2016

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Neuroinflammation is a hallmark of neurodegenerative disorders in the central nerve system (CNS). Thrombin has been known as one of the factors in pathological processes including migration, blood-brain barrier breakdown, brain edema formation, neuroinflammation, and neuronal death. Thrombin has been shown to be a regulator of matrix metalloproteinase (MMPs) expression leading to cell migration. Among MMPs, the elevated expression of MMP-9 has been observed in patients with brain diseases, which may contribute to the pathology of neuroinflammatory and neurodegenerative diseases. However, the mechanisms underlying thrombin-induced MMP-9 expression in SK-N-SH cells were not completely understood. Here, we used gelatin zymography, Western blot, real-time PCR, promoter activity assay, and cell migration assay to demonstrate that thrombin induced the expression of pro-form MMP-9 protein and messenger RNA (mRNA), and promoter activity in SK-N-SH cells, which were attenuated by pretreatment with the pharmacological inhibitor of protease-activated receptor-1 (PAR-1, SCH79797), Gi-coupled receptor (GPA2), c-Src (PP1), Pyk2 (PF431396), EGFR (AG1478), PI3K (LY294002), Akt (SH-5), MEK1/2 (U0126), or AP-1 (TanshinoneIIA) and transfection with small interfering RNA (siRNA) of PAR-1, Gi, c-Src, Pyk2, EGFR, Akt, p44, p42, or c-Jun. Moreover, thrombin-stimulated c-Src, Pyk2, EGFR, Akt, p42/p44 MAPK, or c-Jun phosphorylation was attenuated by their respective inhibitor of PP1, PF431396, AG1478, SH-5, U0126, or TanshinoneIIA. Finally, pretreatment with these inhibitors also blocked thrombin-induced SK-N-SH cell migration. Our results concluded that thrombin binding to PAR-1 receptor activated Gi-protein/c-Src/Pyk2/EGFR/PI3K/Akt/p42/p44 MAPK cascade, which in turn elicited AP-1 activation and ultimately evoked MMP-9 expression and cell migration in SK-N-SH cells.

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Cadmium induces matrix metalloproteinase-9 expression via ROS-dependent EGFR, NF-кB, and AP-1 pathways in human endothelial cells

Cited by 66 publications

References 44 publications

Upregulation of Matrix Metalloproteinase-9 in Primary Cultured Rat Astrocytes Induced by 2-Chloroethanol Via MAPK Signal Pathways

Upregulation of Matrix Metalloproteinase-9 in Primary Cultured Rat Astrocytes Induced by 2-Chloroethanol Via MAPK Signal Pathways

Lysophosphatidic Acid Is Associated with Atherosclerotic Plaque Instability by Regulating NF-κB Dependent Matrix Metalloproteinase-9 Expression via LPA2 in Macrophages

Thrombin Enhanced Matrix Metalloproteinase-9 Expression and Migration of SK-N-SH Cells via PAR-1, c-Src, PYK2, EGFR, Erk1/2 and AP-1

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