IL-13 induces connective tissue growth factor in rat hepatic stellate cells via TGF- independent Smad signaling

Liu, Y; Meyer, Christoph; Mueller, A. J.; Herweck, Frank; Li, Q; Muellenbach, Ralf Michael; Mertens, PR; Dooley, Steven; Weng, Han-Zhuang

doi:10.1055/s-0030-1269479

Cited by 19 publications

(25 citation statements)

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“…However, Smad7, another member of this protein family, abrogates the TGF-β signaling pathway by a regulative negative feedback loop (30), thereby, paving the physiological conditions towards cancer disease manifestation, as HCC is an example when this negative feedback loop is hindered, while the transition to fibrosis, cirhosis and as a consequence HCC is hindered when this negative feedback loop of Smad7 remains active (31). Smad7 is regulated by different signaling pathways (32). IFNγ contributes to this regulatory scheme by inducing a member of the cold shock protein family, the transcription factor YB-1 (30,(70)(71)(72)(73) (Fig.…”

Section: Discussionmentioning

confidence: 99%

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Time- and oxygen-dependent expression and regulation of NDRG1 in human brain cancer cells

et al. 2017

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Abstract. N-myc downstream-regulated gene 1 (NDRG1) is a tumor suppressor with the potential to suppress metastasis, invasion and migration of cancer cells. It is regulated under stress conditions such as starvation or hypoxia. NDRG1 regulation is both induced and controlled by HIF-1α-dependent and -independent pathways under hypoxic conditions. However, there are profound differences in the way NDRG1 expression is regulated by HIF-1α and other transcription factors. Therefore, we aimed to define the time-dependent pattern of NDRG1 mRNA and protein expression in human glioblastoma cell lines in extreme hypoxia and after re-oxygenation as well as under normoxic conditions. Furthermore, we ascribe the regulation of NDRG1 to the transcription factors HIF-1α, SP1, CEBPα, YB-1 and Smad7 in a time-dependent manner. The human malignant glioma cell lines U87-MG, U373 and GaMG were cultured for 1, 6 and 24 h under hypoxic (0.1% O 2 ) conditions and then they were re-oxygenated. The mRNA expression of NDRG1, HIF-1α SP1, CEBPα, YB-1 and Smad7 was measured using semi-quantitative RT-PCR analysis. Their protein expression was analyzed using western blotting. Our experiments revealed that long-term (24 h), but not short-term hypoxia led to the induction of NDRG1 expression in human glioma cell lines. NDRG1 expression was found to correlate with the protein expression of HIF-1α, SP1, CEBPα, YB-1 and Smad7. The present study suggests for the first time that SP1 regulates NDRG1 expression in glioma cells under hypoxia in a time-dependent manner along with HIF-1α, CEBPα, YB-1 and Smad7. These molecules, each separately or in combination, may possess the potential to become target molecules for antitumor therapeutic approaches particularly in human brain tumors.

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Section: Discussionmentioning

confidence: 99%

“…Such a regulation may be involved in the process of cancer manifestation as seen for HCC (31). Smad7 is regulated by different pathways (32). One of these involves the transcription factor YB-1, a member of the cold shock family of proteins (30).…”

Section: Time-and Oxygen-dependent Expression and Regulation Of Ndrg1mentioning

confidence: 99%

Time- and oxygen-dependent expression and regulation of NDRG1 in human brain cancer cells

et al. 2017

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“…Expression of CTGF in HSCs is up-regulated by numerous profibrotic factors, including TGF-␤ (4,18,19), endothelin-1 (20), PDGF-BB, acetaldehyde (21), ethanol (22), and the Th2 cytokine IL-13 (23,24), with TGF-␤ being the most important trigger as elevated TGF-␤ levels are observed in almost all fibrotic liver diseases, irrespective of etiology. Although in vitro experiments have shown that TGF-␤ plays only a minor role in CTGF production in quiescent HSCs (20,23,24), activated HSCs as well as established HSC cell lines secrete high levels of CTGF in response to TGF-␤ treatment (22,23).…”

Section: Connective Tissue Growth Factor (Ctgf)mentioning

confidence: 99%

“…Although in vitro experiments have shown that TGF-␤ plays only a minor role in CTGF production in quiescent HSCs (20,23,24), activated HSCs as well as established HSC cell lines secrete high levels of CTGF in response to TGF-␤ treatment (22,23).…”

Section: Connective Tissue Growth Factor (Ctgf)mentioning

confidence: 99%

Transforming Growth Factor-β (TGF-β)-mediated Connective Tissue Growth Factor (CTGF) Expression in Hepatic Stellate Cells Requires Stat3 Signaling Activation

Liu

Meyer

et al. 2013

Journal of Biological Chemistry

158

135

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“…Hence, the progression of liver fibrosis requires two hits: the presence or activation of the matricellular protein CTGF/CCN2 and the induction of adult tissue injury. Furthermore, up-regulated expression of CTGF/CCN2 by TGF-beindependent signaling such as IL-13 24 and/or by down-regulation of CTGF/CCN2 scavenger low-density lipoprotein-receptor-related protein 1 25 would be critical in fibronectin/TGF-bIIR double-knockout mice to induce liver fibrosis in chronic injury. This latter speculation for the requirement of adult tissue injury is based on evidence that overexpression of CTGF/CCN2 in concert with signaling pathways associated with chronic fibrosing injuries can lead to the initiation or exacerbation of fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Transforming Growth Factor-β–Independent Role of Connective Tissue Growth Factor in the Development of Liver Fibrosis

Sakai

Jawaid

Sasaki

et al. 2014

The American Journal of Pathology

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We previously identified transforming growth factor (TGF)-b signaling as a fibronectin-independent mechanism of type I collagen fibrillogenesis following adult liver injury. To address the contribution of TGF-b signaling during the development of liver fibrosis, we generated adult mice lacking TGF-b type II receptor (TGF-bIIR) from the liver. TGF-bIIR knockout livers indeed showed a dominant effect in reducing fibrosis, but fibrosis still remained approximately 45% compared with control and fibronectin knockout livers. Unexpectedly, this was accompanied by significant up-regulation of connective tissue growth factor mRNA levels. Organized type I collagen networks in TGF-bIIR knockout livers colocalized well with fibronectin. We provide evidence that elimination of TGF-bIIR is not sufficient to completely prevent liver fibrosis. Our results indicate a TGF-beindependent mechanism of type I collagen production and suggest connective tissue growth factor as its potent mediator. We advocate combined elimination of TGF-b signaling and connective tissue growth factor as a potential therapeutic target by which to attenuate liver fibrosis. (Am J Pathol 2014 http://dx

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IL-13 induces connective tissue growth factor in rat hepatic stellate cells via TGF- independent Smad signaling

Cited by 19 publications

References 0 publications

Time- and oxygen-dependent expression and regulation of NDRG1 in human brain cancer cells

Time- and oxygen-dependent expression and regulation of NDRG1 in human brain cancer cells

Transforming Growth Factor-β (TGF-β)-mediated Connective Tissue Growth Factor (CTGF) Expression in Hepatic Stellate Cells Requires Stat3 Signaling Activation

Transforming Growth Factor-β–Independent Role of Connective Tissue Growth Factor in the Development of Liver Fibrosis

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