Hydrogen Peroxide Is a Novel Inducer of Connective Tissue Growth Factor

Park, Sang-Kyu; Kim, Jeong‐A; Seomun, Young; Choi, Jinah; Kim, Dong Hwan; Han, Inn-Oc; Lee, Eunjoo H.; Chung, Sung Kun; Joo, Choun‐Ki

doi:10.1006/bbrc.2001.5058

Cited by 103 publications

(83 citation statements)

References 32 publications

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“…In support of this notion, ROS induced CTGF gene expression in human lens epithelial cells. 52 In addition, CTGF is up-regulated in sclerodermal skin fibroblasts that also release more O 2 and H 2 O 2 in vitro compared to normal fibroblasts. 53,54 Recently Candido et al demonstrated a marked vascular CTGF overexpression in diabetic APO-E knock-out mice, which was inhibited by ACE inhibitor therapy.…”

Section: Discussionmentioning

confidence: 97%

Angiotensin II Induces Connective Tissue Growth Factor Gene Expression via Calcineurin-Dependent Pathways

Finckenberg

Inkinen

Ahonen

et al. 2003

The American Journal of Pathology

102

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Connective tissue growth factor (CTGF) is a polypeptide implicated in the extracellular matrix synthesis.Previous studies have provided evidence that angiotensin II (Ang II) promotes collagen synthesis and regulates collagen degradation. We investigated whether or not CTGF mediates the profibrotic effects of Ang II in the heart and kidneys and the role of calcineurin-dependent pathways in CTGF gene regulation. In transgenic rats harboring human renin and angiotensinogen genes, Ang II induced an age-dependent increase in myocardial CTGF expression, which was 3.5-fold greater compared to normotensive Sprague Dawley (SD) rats. CTGF overexpression correlated closely with the Ang II-induced rise in blood pressure. CTGF mRNA and protein were located predominantly in areas with leukocyte infiltration, myocardial, and vascular lesions and co-localized with TGF␤ 1 , collagen I, and collagen III mRNA expressions. Ang II induced CTGF mRNA and protein to a lesser extent in the kidneys, predominantly in glomeruli, arterioles, and in the interstitium with ample inflammation. However, no expression was found in the right ventricle or pulmonary arteries. Blockade of calcineurin activity by cyclosporine A completely normalized Ang II-induced CTGF overexpression in heart and kidney, suppressed the inflammatory response, and mitigated Ang II-induced cell proliferation and apoptosis. In contrast, blockade of mTOR (target of rapamycin) pathway by everolimus, further increased the expression of CTGF even though everolimus ameliorated cell proliferation and T-cellmediated inflammation. Our findings provide evidence that CTGF mediates Ang II-induced fibrosis in the heart and kidneys via blood pressure and cal-

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Section: Discussionmentioning

confidence: 97%

Angiotensin II Induces Connective Tissue Growth Factor Gene Expression via Calcineurin-Dependent Pathways

Finckenberg

Inkinen

Ahonen

et al. 2003

The American Journal of Pathology

102

View full text Add to dashboard Cite

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“…Also, the promoter of the human heme oxygenase gene which encodes a stress protein that participates in the defense mechanisms against oxidative injury, has a putative STAT3 binding site that contributes to its induction by IL-6 (Deramaudt et al, 1999). Finally, JAK2/3 seem to be involved in the enhanced connective tissue growth factor expression observed after hydrogen peroxide treatment (Park et al, 2001b). These studies suggest that activation of the JAK/STAT signaling cascades assists the cell in surviving oxidative stress situations.…”

Section: Other Signaling Molecules and Pathways Jak/stat Pathwaymentioning

confidence: 89%

Cellular response to oxidative stress: Signaling for suicide and survival*

Martindale

Holbrook

2002

Journal Cellular Physiology

2,086

1,596

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Reactive oxygen species (ROS), whether produced endogenously as a consequence of normal cell functions or derived from external sources, pose a constant threat to cells living in an aerobic environment as they can result in severe damage to DNA, protein, and lipids. The importance of oxidative damage to the pathogenesis of many diseases as well as to degenerative processes of aging has becoming increasingly apparent over the past few years. Cells contain a number of antioxidant defenses to minimize fluctuations in ROS, but ROS generation often exceeds the cell's antioxidant capacity, resulting in a condition termed oxidative stress. Host survival depends upon the ability of cells and tissues to adapt to or resist the stress, and repair or remove damaged molecules or cells. Numerous stress response mechanisms have evolved for these purposes, and they are rapidly activated in response to oxidative insults. Some of the pathways are preferentially linked to enhanced survival, while others are more frequently associated with cell death. Still others have been implicated in both extremes depending on the particular circumstances. In this review, we discuss the various signaling pathways known to be activated in response to oxidative stress in mammalian cells, the mechanisms leading to their activation, and their roles in influencing cell survival. These pathways constitute important avenues for therapeutic interventions aimed at limiting oxidative damage or attenuating its sequelae. Published 2002 Wiley‐Liss, Inc.

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“…Total RNA was prepared by a TRIzol (Invitrogen) method and Northern blot analysis was performed as described previously (Park et al, 2001). Total RNA (10 mg) was denatured and separated on a 1% formaldehyde-agarose gel in MOPs buffer containing 50 mM sodium acetate, MOPs, 2 N NaOH and 0.5 M EDTA (pH 8.0).…”

Section: Rna Isolation and Northern Blottingmentioning

confidence: 99%

Ligand release-independent transactivation of epidermal growth factor receptor by transforming growth factor-β involves multiple signaling pathways

et al. 2007

Oncogene

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Many of the signaling responses induced by transforming growth factor-b (TGF-b) are mediated by Smad proteins, but there is evidence that it can also signal independently of Smads. Here, we provide evidence that multiple signal pathways induced by TGF-b1-including Src family tyrosine kinases (SFKs), generation of reactive oxygen species (ROS), de novo protein synthesis and E-cadherindependent cell-cell interactions-transactivate the epidermal growth factor receptor (EGFR), which in turn regulates expression of c-Fos and c-Jun. Immunoprecipitation and immunofluorescence staining showed that EGFR was phosphorylated on tyrosine in response to TGF-b1. EGFR transactivation required the activation of SFKs and the production of ROS via NADPH oxidase, but was not dependent on metalloproteases or the release of EGF-like ligands. In addition, the production of ROS was dependent on signaling by specific SFKs as well as de novo protein synthesis. Stable transfection of E-cadherin into MDA-MB-231 cells as well as E-cadherin-blocking assays revealed that E-cadherin-mediated cell-cell interactions were also essential for EGFR transactivation. Finally, EGFR transactivation was involved in the expression of c-Fos and c-Jun via the extracellular signal-regulated kinase signaling cascade. Taken together our data suggest that ligand release-independent transactivation of EGFR may diversify early TGF-b signaling and represent a novel pathway leading to TGF-b-mediated gene expression.

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Hydrogen Peroxide Is a Novel Inducer of Connective Tissue Growth Factor

Cited by 103 publications

References 32 publications

Angiotensin II Induces Connective Tissue Growth Factor Gene Expression via Calcineurin-Dependent Pathways

Angiotensin II Induces Connective Tissue Growth Factor Gene Expression via Calcineurin-Dependent Pathways

Cellular response to oxidative stress: Signaling for suicide and survival*

Ligand release-independent transactivation of epidermal growth factor receptor by transforming growth factor-β involves multiple signaling pathways

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