Curcumin inhibits cobalt chloride-induced epithelial-to-mesenchymal transition associated with interference with TGF-β/Smad signaling in hepatocytes

Kong, Desong; Zhang, Feng; Shao, Jiangjuan; Wu, Li; Zhang, Xiaoping; Chen, Li; Lu, Yin; Zheng, Shizhong

doi:10.1038/labinvest.2015.107

Cited by 56 publications

(50 citation statements)

References 27 publications

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“…In the process of EMT, epithelial cells can lose tight junction and get mesenchymal markers in EMT process . Study reported that CCl 4 (0.1 mL/100 g body weight) induced EMT occurrence by up‐regulating the contents of α‐SMA, vimentin, fibronectin, and N‐cadherin, and down‐regulating the level of E‐cadherin in the rat model of liver fibrosis . Our results showed that the protein level of α‐SMA increased and that E‐cadherin content declined, which implied that Nano NiO led to EMT occurrence in rat liver.…”

Section: Discussionmentioning

confidence: 59%

“…TGF‐β1 induces EMT occurrence via Smad‐dependent pathway, while this could be attenuated by baicalin and puerarin in HepG2 cells . Kong et al hold that curcumin inhibits cobalt chloride‐triggered EMT through TGF‐β1/Smad pathway in hepatocytes . TGF‐β1 also brings in EMT by Smad2/3 activation in HepG2 cells .…”

Section: Discussionmentioning

confidence: 99%

“…52 Kong et al hold that curcumin inhibits cobalt chloride-triggered EMT through TGF-β1/Smad pathway in hepatocytes. 49 TGF-β1 also brings in EMT by Smad2/3 activation in HepG2 cells. 56 In the results of our present study, the contents of TGF-β1, p-Smad2, and p-Smad3 increased, while Smad7 decreased in HepG2 cells, which indicated that Nano NiO activated the TGF-β1 and Smad pathway.…”

Section: Effects Of Nano Nio On Tgf-β1 Smad Pathway Emt and Mmp9mentioning

confidence: 97%

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TGF‐β1 mediated Smad signaling pathway and EMT in hepatic fibrosis induced by Nano NiO in vivo and in vitro

Zhang

Chang

Wang

et al. 2019

Environmental Toxicology

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Nickel oxide nanoparticles (Nano NiO) bears hepatotoxicity, while whether it leads to liver fibrosis remains unclear. The aim of this study was to establish the Nano NiO‐induced hepatic fibrosis model in vivo and investigate the roles of transforming growth factor β1 (TGF‐β1) in Smad pathway activation, epithelial‐mesenchymal transition (EMT) occurrence, and extracellular matrix (ECM) deposition in vitro. Male Wistar rats were exposed to 0.015, 0.06, and 0.24 mg/kg Nano NiO by intratracheal instilling twice a week for 9 weeks. HepG2 cells were treated with 100 μg/mL Nano NiO and TGF‐β1 inhibitor (SB431542) to explore the mechanism of collagen formation. Results of Masson staining as well as the elevated levels of type I collagen (Col‐I) and Col‐III suggested that Nano NiO resulted in hepatic fibrosis in rats. Furthermore, Nano NiO increased the protein expression of TGF‐β1, p‐Smad2, p‐Smad3, alpha‐smooth muscle actin (α‐SMA), matrix metalloproteinase9 (MMP9), and tissue inhibitors of metalloproteinase1 (TIMP1), while decreased the protein content of E‐cadherin and Smad7 in rat liver and HepG2 cells. Most importantly, Nano NiO‐triggered the abnormal expression of the abovementioned proteins were all alleviated by co‐treatment with SB431542, implying that TGF‐β1‐mediated Smad pathway, EMT and MMP9/TIMP1 imbalance were involved in overproduction of collagen in HepG2 cells. In conclusion, these findings indicated that Nano NiO induced hepatic fibrosis via TGF‐β1‐mediated Smad pathway activation, EMT occurrence, and ECM deposition.

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Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Section: Effects Of Nano Nio On Tgf-β1 Smad Pathway Emt and Mmp9mentioning

confidence: 97%

See 1 more Smart Citation

TGF‐β1 mediated Smad signaling pathway and EMT in hepatic fibrosis induced by Nano NiO in vivo and in vitro

Zhang

Chang

Wang

et al. 2019

Environmental Toxicology

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“…For example, curcumin inhibits cobalt chloride-induced EMT by regulating TGF-β/Smad signaling in hepatocytes (24), and salvianolic acid B prevents EMT through the TGF-β 1 pathway in vivo and in vitro (25). Our results showed that baicalin and puerarin improved the mesenchymal characteristics through the TGF-β1/Smad3 pathway.…”

Section: Discussionmentioning

confidence: 99%

Baicalin and puerarin reverse epithelial‑mesenchymal transition via the TGF‑β1/Smad3 pathway in�vitro

Liu

Xing

et al. 2018

Exp Ther Med

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Epithelial-mesenchymal transition (EMT) occurs in the development of fibrosis and carcinogenesis. EMT is associated with chronic liver injury. Evidence shows that hepatocytes undergo EMT in the adult liver. The Qinggan Huoxue Recipe (QGHXR), a Traditional Chinese Medicinal formula, shows a range of pharmacological effects in treating alcoholic liver disease. The present study aimed to investigate the effect of four major components of QGHXR, baicalin, salvianic acid, puerarin and saikosaponin, on EMT in vitro, and to elucidate the potential mechanism of QGHXR against EMT via the transforming growth factor-β1 (TGF-β1)/Smads signaling pathway. EMT models were established using LO2 hepatocytes and HepG2 cells treated with acetaldehyde in vitro. Acetaldehyde presented a mesenchymal cell characteristic in hepatocytes, accompanied by an increased expression of mesenchymal markers, including vimentin and fibronectin, and decreased E-cadherin. Baicalin and puerarin abrogated the increased expression of vimentin and fibronectin, and rescued E-cadherin expression in acetaldehyde-treated hepatocytes. It was further demonstrated that baicalin and puerarin reduced the gene expression of snail, TGF-β1 and Smad3. A decreased expression of tight function markers, including ZO-1, occludin and claudin, were also found in the acetaldehyde-treated hepatocytes. Barcacin regulated the mRNA level of TGF-βl and snail, and then suppressed the EMT process. This was accompanied by an increased mRNA level of E-cadherin and decreased levels of vimentin and fibronectin, but no significant differences in of Smad3, occludin, ZO-1 and claudin were observed. Puerarin regulated the mRNA level of TGF-βl, Smad3 and snail, suppresing the EMT process, which was accompanied by an increased mRNA level of E-cadherin and decreased levels of vimentin and fibronectin, along with increased levels of occludin, ZO-1 and claudin. When the snail gene was silent, barcacin and puerarin did not show significant effects in the acetaldehyde-treated cells. The results presented a novel mechanism through which baicalin and puerarin modulated hepatocyte EMT to improve liver fibrosis.

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“…Liver fibrosis was traditionally believed to be caused by excessive extracellular matrix (ECM) production of hepatic stellate cells (HSCs) (Fang et al, 2014;Gortzen et al, 2015;Hong et al, 2015). However, a recent study has shown that the occurrence of EMT in hepatocytes also contributed to liver fibrosis (Kong et al, 2015). Hepatocytes acquiring mesenchymal properties could synthesize and release extracellular matrix (ECM) under the condition of oxidative stress (Kong et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Advanced oxidation protein products induce hepatocyte epithelial–mesenchymal transition via a ROS‐dependent, TGF‐β/Smad signaling pathway

Sun

Xie

Zhang

et al. 2017

Cell Biology International

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Epithelial-mesenchymal transition (EMT) occurs during the progression of liver fibrosis in response to chronic liver injury. However, the molecular mechanism underlying the regulation of hepatocyte EMT remains unclear. The aim of this study was to determine whether advanced oxidation protein products (AOPP) had an effect on hepatocyte EMT. The human L02 hepatocyte cell line and hepatocytes from normal Sprague-Dawley rats were challenged with AOPP treatment in both in vitro and in vivo studies. The expression of cell and molecular markers of EMT in L02 hepatocytes were studied using Western blotting, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assays. Hepatocyte migratory potential was analyzed using a wound healing assay. Intracellular reactive oxygen species (ROS) were detected using the dichlorofluorescein (DCF) assay. In liver tissue sections, expression of EMT markers was evaluated using immunohistochemistry, and collagen was assessed using histochemical staining with Masson's trichrome. The findings were that AOPP treatment resulted in EMT in hepatocytes, which was associated with reduced expression of E-cadherin, increased expression of vimentin, increased deposition of collagen protein, and enhanced cell migration in vivo and in vitro. AOPP was also found to promote migration in L02 cells, and to promote the production of ROS and the activation of TGF-βR and Smad signaling. Inhibition of the generation of intracellular ROS and TGF-β receptor blocking could reverse AOPP-induced EMT in hepatocytes. This study has identified a novel mechanism in the regulation of hepatocyte EMT, and the findings may have implications for the control of liver fibrosis.

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Curcumin inhibits cobalt chloride-induced epithelial-to-mesenchymal transition associated with interference with TGF-β/Smad signaling in hepatocytes

Cited by 56 publications

References 27 publications

TGF‐β1 mediated Smad signaling pathway and EMT in hepatic fibrosis induced by Nano NiO in vivo and in vitro

TGF‐β1 mediated Smad signaling pathway and EMT in hepatic fibrosis induced by Nano NiO in vivo and in vitro

Baicalin and puerarin reverse epithelial‑mesenchymal transition via the TGF‑β1/Smad3 pathway in�vitro

Advanced oxidation protein products induce hepatocyte epithelial–mesenchymal transition via a ROS‐dependent, TGF‐β/Smad signaling pathway

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