c-Src-dependent MAPKs/AP-1 activation is involved in TNF-α-induced matrix metalloproteinase-9 expression in rat heart-derived H9c2 cells

Yang, Che‐Hua; Lee, I-Te; Lin, Chih Chung; Wang, Chao Hung; Cherng, Wen Jin; Hsiao, Li Der

doi:10.1016/j.bcp.2013.01.013

Cited by 37 publications

(55 citation statements)

References 34 publications

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“…c-Src did not alter CSEinduced MMP-1 release ( Figure E6). Other researchers have observed that MMP-9 regulation could be c-Src dependent (20); however, our data establish that Src is a critical regulator of MMP-9 in smoke conditions and highlight the potential of cSrc inhibitors to counteract the induction of this key mediator in cancer and COPD (21,22). AZD-0530 or silencing of c-Src/c-Raf/ KRAS also prevented CSE-induced IL-1b and IL-6 secretions from SAE cells ( Figure 2F).…”

Section: Azd0530 Inhibits C-src Activation In Sae Cells Isolated Frommentioning

confidence: 96%

Cigarette Smoke Activates the Proto-Oncogene c-Src to Promote Airway Inflammation and Lung Tissue Destruction

Geraghty

Hardigan

Foronjy

2014

Am J Respir Cell Mol Biol

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The diagnosis of chronic obstructive pulmonary disease (COPD) confers a 2-fold increased lung cancer risk even after adjusting for cigarette smoking, suggesting that common pathways are operative in both diseases. Although the role of the tyrosine kinase c-Src is established in lung cancer, less is known about its impact in other lung diseases, such as COPD. This study examined whether c-Src activation by cigarette smoke contributes to the pathogenesis of COPD. Cigarette smoke increased c-Src activity in human small airway epithelial (SAE) cells from healthy donors and in the lungs of exposed mice. Similarly, higher c-Src activation was measured in SAE cells from patients with COPD compared with healthy control subjects. In SAE cells, c-Src silencing or chemical inhibition prevented epidermal growth factor (EGF) receptor signaling in response to cigarette smoke but not EGF stimulation. Further studies showed that cigarette smoke acted through protein kinase C a to trigger c-Src to phosphorylate EGF receptor and thereby to induce mitogen-activated protein kinase responses in these cells. To further investigate the role of c-Src, A/J mice were orally administered the specific Src inhibitor AZD-0530 while they were exposed to cigarette smoke for 2 months. AZD-0530 treatment blocked c-Src activation, decreased macrophage influx, and prevented airspace enlargement in the lungs of cigarette smoke-exposed mice.Moreover, inhibiting Src deterred the cigarette smoke-mediated induction of matrix metalloproteinase-9 and -12 in alveolar macrophages and lung expression of cathepsin K, IL-17, TNF-a, MCP-1, and KC, all key factors in the pathogenesis of COPD. These results indicate that activation of the proto-oncogene c-Src by cigarette smoke promotes processes linked to the development of COPD.

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Section: Azd0530 Inhibits C-src Activation In Sae Cells Isolated Frommentioning

confidence: 96%

Cigarette Smoke Activates the Proto-Oncogene c-Src to Promote Airway Inflammation and Lung Tissue Destruction

Geraghty

Hardigan

Foronjy

2014

Am J Respir Cell Mol Biol

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“…Consistently, our previous data demonstrate that the migratory response of neural stem cells to SDF-1a showed a typical biphasic dose-response curve (Chen et al 2014). All these findings indicate that MSCs at varying levels of Many studies have shown that PI3K/Akt and MAPK signaling pathways mediate cell migration induced by chemokines or cytokines (Bullone et al 2013;Yang et al 2013;Segarra et al 2006). In the present study, we found that SDF1a altered the phosphorylation of Akt and MAPKs which correlate closely with the differentiation states of MSCs.…”

Section: Discussionmentioning

confidence: 91%

Neural Differentiation of Mesenchymal Stem Cells Influences Their Chemotactic Responses to Stromal Cell-Derived Factor-1α

Xie

et al. 2014

Cell Mol Neurobiol

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Mesenchymal stem cells (MSCs) are proposed as a promising source for cell-based therapies in neural disease. Although increasing numbers of studies have been devoted to the delineation of factors involved in the migration of MSCs, the relationship between the chemotactic response and the differentiation status of these cells is still unclear. In the present study, we demonstrated that MSCs in varying neural differentiation states display various chemotactic responses to stromal cell-derived factor-1α (SDF-1α). The chemotactic responses of MSCs under different differentiation stages in response to SDF-1α were analyzed by Boyden chamber, and the results showed that cells of undifferentiation, 24-h preinduction, 5-h induction, and 18-h maintenance states displayed a stronger chemotactic response to SDF-1α, while 48-h maintenance did not. Further, we found that the phosphorylation levels of PI3K/Akt, ERK1/2, SAPK/JNK, and p38MAPK are closely related to the differentiation states of MSCs subjected to SDF-1α, and finally, inhibition of SAPK/JNK signaling significantly attenuates SDF-1α-stimulated transfilter migration of MSCs of undifferentiation, 24-h preinduction, 18-h maintenance, and 48-h maintenance, but not MSCs of 5-h induction. Meanwhile, interference with PI3K/Akt, p38MAPK, or ERK1/2 signaling prevents only cells at certain differentiation state from migrating in response to SDF-1α. Collectively, these results demonstrate that MSCs in varying neural differentiation states have different migratory capacities, thereby illuminating optimization of the therapeutic potential of MSCs to be used for neural regeneration after injury.

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“…The activities of pro-MMP-2 and MMP-2 are increased in DCM while MMP-9 activity shows only a tendency for an increase (Papazafiropoulou et al, 2010), which is also accompanied by an increase in MMP-1 activity. A number of studies have shown that the TNF-a-induced activation of NF-kB and JNK/AP-1 signaling pathways and upregulation of MMP-9 expression can induce apoptosis in H9c2 cells and cardiovascular inflammation (Wu et al, 2013;Chen et al, 2013b;Yang et al, 2013). In a diabetic state, elevated levels of cytokines (such as TGF-b1, TNF-a) and accumulation of free radicals of oxygen can promote the activation of MMPs.…”

Section: Discussionmentioning

confidence: 99%

Cardiac damage and dysfunction in diabetic cardiomyopathy are ameliorated by Grx1

Gao

et al. 2016

Genet. Mol. Res.

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ABSTRACT. Glutaredoxin 1 (Grx1) has been found to be an important endogenous antioxidant enzyme closely related to the pathogenesis of diabetes and cardiovascular diseases caused by oxidative stress. In this study, the functional changes of the Grx1 redox system in blood of hyperglycemic patients were examined. Furthermore, using a rat model of streptozotocin (STZ)-and high-fat-diet-induced type 2 diabetes, we explored the correlation between functional changes of the Grx1 redox system in the left ventricular tissue and blood of the diabetic rats. Moreover, we studied the protective effect of Grx1 against cardiac toxicity caused by the high-glucose-induced expression of cardiac matrix metalloproteinases (MMPs) in primary cultured cardiac fibroblasts. Finally, we investigated the protective effects and signaling regulatory mechanism of Grx1 against diabetic cardiomyopathy (DCM) in terms of oxidative stress and NF-kB-mediated fibrosis-associated signaling pathways. In the serum of hyperglycemic patients, Grx1 levels were elevated, total/protein thiol or sulfhydryl (Total-SH/P-SH) levels were decreased, glutathione was downregulated, and oxidized glutathione was upregulated. In addition, in the left ventricular myocardium and blood of the diabetic rats, Grx1 levels were significantly increased and glutathione reductase and P-SH levels were decreased. Moreover, endogenous Grx1 was highly expressed in cardiac fibroblasts during high-glucose treatment, and exogenous Grx1 can prevent DCM by controlling oxidative damage and MMP expression. These findings are suggestive of changes in the Grx1 redox system, and Grx1-regulated protein oxidative modifications may serve as molecular markers for diabetes caused by high-glucose-induced oxidative stress.

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c-Src-dependent MAPKs/AP-1 activation is involved in TNF-α-induced matrix metalloproteinase-9 expression in rat heart-derived H9c2 cells

Cited by 37 publications

References 34 publications

Cigarette Smoke Activates the Proto-Oncogene c-Src to Promote Airway Inflammation and Lung Tissue Destruction

Cigarette Smoke Activates the Proto-Oncogene c-Src to Promote Airway Inflammation and Lung Tissue Destruction

Neural Differentiation of Mesenchymal Stem Cells Influences Their Chemotactic Responses to Stromal Cell-Derived Factor-1α

Cardiac damage and dysfunction in diabetic cardiomyopathy are ameliorated by Grx1

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