Transforming growth factor-β gene silencing using adenovirus expressing TGF-β1 or TGF-β2 shRNA

Oh, Sejong; Kim, E.; Kang, Dong Zhou; Kim, M.; Kim, J. H.; Song, Jae J.

doi:10.1038/cgt.2012.90

Cited by 18 publications

(14 citation statements)

References 31 publications

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“…These results are in agreement with those recently reported for cells from human skin melanoma (17). However, the underlying mechanism of TGF-␤1 controlling the endogenous levels of TGF-␤2 is currently not understood.…”

Section: Discussionsupporting

confidence: 83%

“…2A and B). This finding was in accordance with previously reported data (17). We then tested whether downregulation of TGF-␤1 and TGF-␤2 changed the protein levels of VE-cadherin, ␣-SMA, and fibronectin.…”

Section: Endotoxin Induces the Expression Of Tgf-␤1 And Tgf-␤2supporting

confidence: 78%

“…In human prostate adenocarcinoma cells, it has been shown that inhibition of TGF-␤1 expression also decreases the expression of TGF-␤2 and that the expression of TGF-␤1 is suppressed by siTGF␤2 (17). These different results suggest that the control exerted by a single TGF-␤ isoform on another isoform may be dependent on the specific cell type where the process occurs.…”

Section: Discussionmentioning

confidence: 49%

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Endotoxin-Induced Endothelial Fibrosis Is Dependent on Expression of Transforming Growth Factors β1 and β2

et al. 2014

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f During endotoxemia-induced inflammatory disease, bacterial endotoxins circulate in the bloodstream and interact with endothelial cells (ECs), inducing dysfunction of the ECs. We previously reported that endotoxins induce the conversion of ECs into activated fibroblasts. Through endotoxin-induced endothelial fibrosis, ECs change their morphology and their protein expression pattern, thereby suppressing endothelial markers and upregulating fibrotic proteins. The most commonly used fibrotic inducers are transforming growth factor ␤1 (TGF-␤1) and TGF-␤2. However, whether TGF-␤1 and TGF-␤2 participate in endotoxin-induced endothelial fibrosis remains unknown. We have shown that the endotoxin-induced endothelial fibrosis process is dependent on the TGF-␤ receptor, ALK5, and the activation of Smad3, a protein that is activated by ALK5 activation, thus suggesting that endotoxin elicits TGF-␤ production to mediate endotoxin-induced endothelial fibrosis. Therefore, we investigated the dependence of endotoxin-induced endothelial fibrosis on the expression of TGF-␤1 and TGF-␤2. Endotoxin-treated ECs induced the expression and secretion of TGF-␤1 and TGF-␤2. TGF-␤1 and TGF-␤2 downregulation inhibited the endotoxininduced changes in the endothelial marker VE-cadherin and in the fibrotic proteins ␣-SMA and fibronectin. Thus, endotoxin induces the production of TGF-␤1 and TGF-␤2 as a mechanism to promote endotoxin-induced endothelial fibrosis. To the best of our knowledge, this is the first report showing that endotoxin induces endothelial fibrosis via TGF-␤ secretion, which represents an emerging source of vascular dysfunction. These findings contribute to understanding the molecular mechanism of endotoxin-induced endothelial fibrosis, which could be useful in the treatment of inflammatory diseases.

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Section: Discussionsupporting

confidence: 83%

Section: Endotoxin Induces the Expression Of Tgf-␤1 And Tgf-␤2supporting

confidence: 78%

Section: Discussionmentioning

confidence: 49%

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Endotoxin-Induced Endothelial Fibrosis Is Dependent on Expression of Transforming Growth Factors β1 and β2

et al. 2014

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“…This finding was in accordance with previously reported data. 55 However, the action of siTGFb2 did not affect the expression of TGF-b1 (Supplementary Figure S4a). Then, we tested whether the downregulation of TGF-b1 and TGF-b2 in the absence of any stimulus changed the protein levels of VE-cadherin, a-SMA, and fibronectin.…”

Section: H 2 O 2 -Induced Conversion Of Ecs Into Myofibroblasts Is Dementioning

confidence: 99%

Oxidative stress mediates the conversion of endothelial cells into myofibroblasts via a TGF-β1 and TGF-β2-dependent pathway

Montorfano

Becerra

Cerro

et al. 2014

Laboratory Investigation

120

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During the pathogenesis of systemic inflammation, reactive oxygen species (ROS) circulate in the bloodstream and interact with endothelial cells (ECs), increasing intracellular oxidative stress. Although endothelial dysfunction is crucial in the pathogenesis of systemic inflammation, little is known about the effects of oxidative stress on endothelial dysfunction. Oxidative stress induces several functions, including cellular transformation. A singular process of cell conversion is tendothelial-to-mesenchymal transition, in which ECs become myofibroblasts, thus losing their endothelial properties and gaining fibrotic behavior. However, the participation of oxidative stress as an inductor of conversion of ECs into myofibroblasts is not known. Thus, we studied the role played by oxidative stress in this conversion and investigated the underlying mechanism. Our results show that oxidative stress induces conversion of ECs into myofibroblasts through decreasing the levels of endothelial markers and increasing those of fibrotic and ECM proteins. The underlying mechanism depends on the ALK5/Smad3/NF-kB pathway. Oxidative stress induces the expression and secretion of TGF-b1 and TGF-b2 and p38 MAPK phosphorylation. Downregulation of TGF-b1 and TGF-b2 by siRNA technology abolished the H 2 O 2 -induced conversion. To our knowledge, this is the first report showing that oxidative stress is able to induce conversion of ECs into myofibroblasts via TGF-b secretion, emerging as a source for oxidative stress-based vascular dysfunction. Thus, oxidative stress emerges as a decisive factor in inducing conversion of ECs into myofibroblasts through a TGF-b-dependent mechanism, changing the ECs protein expression profile, and converting normal ECs into pathological ones. This information will be useful in designing new and improved therapeutic strategies against oxidative stress-mediated systemic inflammatory diseases.

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“…Overexpression of TGF-β1 in tumor cells provides additional oncogenic activities by circumventing the host immune surveillance (Oh et al, 2013). In liver diseases, the persistence of chronic inflammation, as observed in chronic viral hepatitis, plays a major role in determining the shift in the TGF-β1 signaling pathway from tumor suppression to increasing the risk of HCC (Lu et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

TGF-β1 polymorphism 509 C>T is associated with an increased risk for hepatocellular carcinoma in HCV-infected patients

Ma¹,

Liu²,

Fang³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Transforming growth factor-beta 1 (TGF-β1), a member of the transforming growth factor beta family, functions as a multi-functional cytokine and plays a key role in cellular growth, proliferation, and differentiation. The 509 C/T polymorphism in the TGF-β1 gene has been implicated in the outcome of hepatitis C virus (HCV) infection; however, little is known regarding the relationship between TGF-β1 gene mutations and the development of hepatocellular carcinoma (HCC) in HCV-infected patients. The aim of the study was to evaluate the effect of the TGF-β1 polymorphisms 509 C>T on the occurrence of HCC in patients chronically infected with HCV in a Chinese Han population. The results showed that HCC patients had a higher frequency of the TGF-β1 -509 TT genotype distribution of the TGF-β1 -509 polymorphism and a lower frequency of the CC genotype. Serum TGF-β1 levels were significantly higher in patients with the TT genotype than in those with the CC genotype. In this study, we confirmed that the TGF-β1 polymorphism 509 C>T is associated with the risk of HCC in HCV-infected patients.

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Transforming growth factor-β gene silencing using adenovirus expressing TGF-β1 or TGF-β2 shRNA

Cited by 18 publications

References 31 publications

Endotoxin-Induced Endothelial Fibrosis Is Dependent on Expression of Transforming Growth Factors β1 and β2

Endotoxin-Induced Endothelial Fibrosis Is Dependent on Expression of Transforming Growth Factors β1 and β2

Oxidative stress mediates the conversion of endothelial cells into myofibroblasts via a TGF-β1 and TGF-β2-dependent pathway

TGF-β1 polymorphism 509 C>T is associated with an increased risk for hepatocellular carcinoma in HCV-infected patients

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