Emodin inhibits TNF α-induced MMP-1 expression through suppression of activator protein-1 (AP-1)

Lee, Jongsung; Jung, Eunsun; Lee, Ji-Young; Huh, Sungran; Hwang, Cheng-Hwan; Lee, Hwa Young; Kim, Eun-Jung; Cheon, Jimin; Hyun, Chang Gu; Kim, Yeong Shik; Park, Deokhoon

doi:10.1016/j.lfs.2006.08.008

Cited by 46 publications

(39 citation statements)

References 28 publications

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“…Emodin also inhibits TGF-β1-induced tissue inhibitors of metalloproteinase (TIMP-1) by suppressing activated protein-1 (AP-1) and ERK1/2 phosphorylation in hepatic stellate cells (19), and attenuates the pulmonary fibrosis process in bleomycin-treated mice and decreases fibroblast proliferation and collagen production (3). Emodin additionally suppresses TNF-α-induced matrix metalloproteinases by blocking the AP-1 signal, as well as by inhibiting ERK and JNK phosphorylation (20).…”

Section: Discussionmentioning

confidence: 99%

“…In the present study, the suppression of p38 and ERK1/2 signaling by their specific inhibitors significantly suppressed TGF-β1-induced fibronectin and collagen III secretion, but JNK inhibition did not significantly alter ECM expression, suggesting that TGF-β1 promotes ECM synthesis by activating the ERK1/2 and p38 pathways, but not the JNK pathway. Emodin has been demonstrated to attenuate MAPK activation in various types of cells (4,19,20). It suppresses ERK and JNK signals in HSC5 and MDA-MB-231 cells (23), and also attenuates TNF-α-induced JNK activation in human subconjunctival fibroblasts (24).…”

Section: Discussionmentioning

confidence: 99%

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Emodin inhibits extracellular matrix synthesis by suppressing p38 and ERK1/2 pathways in TGF-β1-stimulated NRK-49F cells

et al. 2011

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Abstract. emodin has been demonstrated to inhibit the fibrotic process in chronic renal disease, but its mechanisms have yet to be fully elucidated. This study was carried out to investigate the effects of emodin on extracellular matrix (ecM) synthesis in TGF-β1-stimulated NRK-49F cells. NRK-49F cells stimulated with TGF-β1 were incubated with various concentrations of emodin. ECM proteins, including collagen type III and fibronectin, were detected using ELISA. ERK1/2, p38 and JNK phosphorylation were measured by Western blotting. p38, ERK1/2 and JNK were respectively inhibited with the specific inhibitors SB203580, PD98059 and SP600125. Emodin slightly inhibited the expression of fibronectin and collagen type III in NRK-49F cells without TGF-β1 treatment, and significantly suppressed fibronectin and collagen type III secretion in TGF-β1-stimulated NRK-49F cells. ERK1/2 and p38 specific inhibitors, but not JNK inhibitor, suppressed the TGF-β1-induced expression of fibronectin and collagen type III. Our previous study demonstrated that there was no crosstalk between ERK1/2, p38 and JNK signals in TGF-β1-stimulated NRK-49F cells. Here, we found that emodin inhibited the phosphorylation of ERK1/2 and p38 significantly, but did not suppress the phosphorylation of JNK. In summary, emodin suppresses fibronectin and collagen type III expression via the inhibition of ERK1/2 and p38 phosphorylation in TGF-β1-stimulated NRK-49F cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Emodin inhibits extracellular matrix synthesis by suppressing p38 and ERK1/2 pathways in TGF-β1-stimulated NRK-49F cells

et al. 2011

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“…TNF alpha-induced and heat-induced MMP-1 expression is mediated through ERK1/2 and JNK activation 15,35 .…”

Section: Discussionmentioning

confidence: 99%

“…Expression of the interstitial collagenase (MMP-1) is mediated through activator protein-1 (AP-1) 15,16 . The proximal AP-1 element located between −72 and −66 of MMP-1 promoter region plays a major role in the transcriptional regulation of MMP-1 gene expression [16][17][18] .…”

Section: Introductionmentioning

confidence: 99%

Cholesterol, a Major Component of Caveolae, Down-regulates Matrix Metalloproteinase-1 Expression through ERK/JNK Pathway in Cultured Human Dermal Fibroblasts

et al. 2010

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Background: Cholesterol is a major component of specialized membrane microdomains known as lipid rafts or caveolae, which modulate the fluidity of biological membranes. Membrane cholesterol therefore plays an important role in cell signaling and vesicular transport. Objective: In this study, we investigated the effects of cholesterol on matrix metalloproteinase-1 (MMP-1) expression in human dermal fibroblasts. Methods: MMP-1 mRNA and protein expression were determined by RT-PCR and Western blotting, respectively. AP-1 DNA binding activity was detected by electrophoretic mobility shift assays. The amount of cholesterol was analyzed by cholesterol assay kit. Results: We observed that MMP-1 mRNA and protein expression was dose-dependently decreased by cholesterol treatment. In contrast, cholesterol depletion by a cholesterol depletion agent, methyl-beta-cyclodextrin (MβCD) in human dermal fibroblasts, increased MMP-1 mRNA and protein expression in a dose-dependent manner. Also, we investigated the regulatory mechanism of MβCD-induced MMP-1 expression: cholesterol depletion by MβCD, activated ERK1/2 and JNK, but not p38 MAPK cascade, and it also significantly increased c-Jun phosphorylation, c-Fos expression and activator protein-1 binding activity. Furthermore, the inhibition of ERK or JNK with specific chemical inhibitors prevented MβCD-induced MMP-1 expression, which indicates that ERK and JNK play an important role in cholesterol depletion-mediated MMP-1 induction. In addition, MβCD-induced phosphorylation of ERK and JNK and MMP-1 expression were suppressed by cholesterol repletion. Conclusion: Our results suggest that cholesterol regulates MMP-1 expression through the control of ERK and JNK activity in human dermal fibroblasts. (Ann Dermatol 22(4) 379∼388, 2010)

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“…MAPKs contain three general classes: ERK, JNK, and p38 MAPKs, mediating AP-1 activation. Activation of MAPKs occurs through the phosphorylation of specific threonines and tyrosines, and the components of AP-1 are phosphorylated after the activated MAPKs translocate to the nucleus (36). In this study, we found that trans-Zeatin inhibits UVB-induced activation of ERK, JNK and p38 MAPKs (Fig.…”

Section: Discussionmentioning

confidence: 50%

Trans-Zeatin inhibits UVB-induced matrix metalloproteinase-1 expression via MAP kinase signaling in human skin fibroblasts

Yang

Ji²,

Kang³

et al. 2009

Int J Mol Med

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Abstract. Ultraviolet (UV) irradiation induces the expression of matrix metalloproteinases (MMPs), disturbing the metabolism of extracellular matrix (ECM), and causes the characteristic changes of photoaging in skin. Inhibition of induction of MMPs is suggested to alleviate photoaging induced by UV irradiation. Zeatin, purified from Zea mays, is a member of the cytokinin group of plant growth factors, the activity of which is attributed to its more stable trans form. In this study, we investigated the effect of trans-Zeatin on UVBinduced matrix metalloproteinase-1 (MMP-1) expression in cultured human skin fibroblasts (HSFs) and studied the mechanisms of its actions. We found that pretreatment with trans-Zeatin significantly inhibits UVB-induced MMP-1 expression and c-Jun activation in a dose-dependent manner. We also observed that trans-Zeatin inhibits UVB-induced phosphorylation of ERK, JNK and p38 MAP kinases (MAPKs) dose-dependently. As expected, PD98059, an ERK inhibitor, SP600125, a JNK inhibitor and SB203580, a p38 MAPK inhibitor effectively inhibit UVB-induced phosphorylation of ERK, JNK and p38 MAPKs, respectively. Moreover, the inhibitory mechanism of trans-Zeatin was further demonstrated in MMP-1 secretion using MAPK-specific inhibitors. PD98059, SP600125 and SB203580 suppressed UVB-induced MMP-1 secretion, which is consistent with the above results. Collectively, our results suggest that trans-Zeatin inhibits UVB-induced MMP-1 expression, which may be mediated by inhibition of ERK, JNK and p38 MAPKs signaling pathways in HSFs. Trans-Zeatin is a potential agent for the management of skin photoaging.

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Emodin inhibits TNF α-induced MMP-1 expression through suppression of activator protein-1 (AP-1)

Cited by 46 publications

References 28 publications

Emodin inhibits extracellular matrix synthesis by suppressing p38 and ERK1/2 pathways in TGF-β1-stimulated NRK-49F cells

Emodin inhibits extracellular matrix synthesis by suppressing p38 and ERK1/2 pathways in TGF-β1-stimulated NRK-49F cells

Cholesterol, a Major Component of Caveolae, Down-regulates Matrix Metalloproteinase-1 Expression through ERK/JNK Pathway in Cultured Human Dermal Fibroblasts

Trans-Zeatin inhibits UVB-induced matrix metalloproteinase-1 expression via MAP kinase signaling in human skin fibroblasts

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