Side population in <scp>LX2</scp> cells decreased by transforming growth factor‐β

Kim, Jong Bin; Ann, Yeon Hwa; Park, Seo Young; Jee, Hyeon Gun; Kim, Hye Ri; Lee, Jeong Hoon; Yu, Su Jong; Lee, Hyo Suk; Kim, Yoon Jun

doi:10.1111/hepr.12106

Cited by 4 publications

(2 citation statements)

References 34 publications

(78 reference statements)

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“…In addition, TGF-β induces differentiation of quiescent hepatic stellate cells into activated cells in the liver (8), fibrosis through extracellular matrix (ECM) deposition and HCC (9). TGF-β binds several proteins, activates several signaling pathways and is involved in HCC progression (10).…”

Section: Introductionmentioning

confidence: 99%

Transforming growth factor‑β decreases side population cells in hepatocellular carcinoma inï¿½vitro

et al. 2018

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Abstract. Hepatocellular carcinoma (HCC) can result from hepatitis B or C infection, fibrosis or cirrhosis. Transforming growth factor-β (TGF-β) is one of the main growth factors associated with fibrosis or cirrhosis progression in the liver, but its role is controversial in hepatocarcinogenesis. In the present study, the effect of TGF-β on the HCC Huh-7 and Huh-Bat cell lines was evaluated. To study the effect of TGF-β, Huh-7 and Huh-Bat cells were treated with TGF-β and a TGF-β receptor inhibitor (SB431542). Cell survival, cell cycle, numbers of side population (SP) cells and expression of the cancer stem cell marker cluster of differentiation (CD)133, epithelial-mesenchymal transition markers (E-cadherin, α-smooth muscle actin and vimentin) and TGF-β-regulated proteins [phospho-c-Jun N-terminal kinase (p-JNK), p-c-Jun and p-smad2] were investigated. TGF-β treatment resulted in decreased cell survival with a targeted effect on SP cells. Expression of CD133 and vimentin was upregulated by treatment with the TGF-β receptor antagonist SB431542, but not with TGF-β. By contrast, TGF-β induced accumulation of cells at G0/G1, and upregulated expression of p-JNK, p-c-Jun and p-smad2. However, these effects were blocked when cells were treated with TGF-β plus SB431542, indicating the specificity of the TGF-β effect. The present results indicated that TGF-β has anticancer effects mediated by survival inhibition of cancer stem cells, which may be developed as a novel therapy for HCC.

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Section: Introductionmentioning

confidence: 99%

Transforming growth factor‑β decreases side population cells in hepatocellular carcinoma inï¿½vitro

et al. 2018

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“…Activated hepatic stellate cells (HSCs) are known to participate in ECM remodeling by producing various types of collagen, MMPs, TIMPs, and TGF-β1, thus deeply influencing fibrotic progression and regression (8,9). Numerous studies have indicated that the activation of HSCs is the cytological basis and the main initiator of hepatic fibrosis (10)(11)(12)(13). Consequently, the inhibition of HSC proliferation has become an important antifibrotic therapeutic strategy.…”

Section: Introductionmentioning

confidence: 99%

Effects of small interfering RNA-mediated downregulation of the Krüppel-like factor 4 gene on collagen metabolism in human hepatic stellate cells

Niu²,

et al. 2015

Molecular Medicine Reports

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The nuclear transcription factor Krüppel-like factor 4 (KLF4) has an important role in cellular biological processes. However, the influence of KLF4 on collagen metabolism remains to be elucidated. In the present study, the effects and underlying mechanism of action of KLF4 on collagen metabolism was investigated in human hepatic stellate cells (HSC), by downregulating KLF4 expression using small interfering RNA (siRNA). The effects of KLF4 silencing by three predesigned siRNAs (siRNA1‑3) were evaluated using both reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blotting in the human LX2 HSC line. The mRNA expression levels of KLF4 were decreased by ~34, 40, and 69% in the siRNA1, siRNA2, and siRNA3 groups, respectively, as compared with the control group. These results were concordant with the protein expression levels of KLF4, as determined by western blot analysis. In the siRNA3 group, the quantity of type Ⅰ and type III collagen, and the expression levels of collagen metabolism proteins including matrix metalloproteinase‑1 (MMP‑1) and tissue inhibitors of metalloproteinases‑1 (TIMP‑1), were determined using both RT‑qPCR and western blotting. Both the mRNA and protein expression levels of type I and type III collagen were significantly decreased in the siRNA3 group, as compared with the control group. The mRNA and protein expression levels of TIMP‑1 were also significantly reduced in the siRNA3‑treated cells, whereas the mRNA and protein expression levels of MMP‑1 were significantly upregulated. Furthermore, KLF4 gene silencing significantly decreased the expression levels of numerous cytokines, including transforming grow factor‑β1, tumor necrosis factor‑α, and interleukin‑1β. The results of the present study provide evidence of siRNA‑mediated silencing of KLF4 expression, which may promote extracellular matrix (ECM) degradation, and inhibition of ECM synthesis. Therefore, KLF4 may be a promising target for the development of novel antifibrotic therapies.

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Side Population

Behbod

Vivanco

2015

Methods in Molecular Biology

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Side population in LX2 cells decreased by transforming growth factor‐β

Abstract: These results show that LX2 cells contain an SP fraction and that TGF-β signaling is involved in the induction of ECM deposition as well as the number of SP cells.

Cited by 4 publications

References 34 publications

Transforming growth factor‑β decreases side population cells in hepatocellular carcinoma inï¿½vitro

Transforming growth factor‑β decreases side population cells in hepatocellular carcinoma inï¿½vitro

Effects of small interfering RNA-mediated downregulation of the Krüppel-like factor 4 gene on collagen metabolism in human hepatic stellate cells

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