Triptolide suppresses paraquat induced idiopathic pulmonary fibrosis by inhibiting TGFB1-dependent epithelial mesenchymal transition

Chen, Hong; Chen, Qun; Jiang, Chunming; Shi, Guangyue; Sui, Bowen; Zhang, Wei; Yang, Lizhen; Li, Zhuying; Liu, Li; Su, Y F; Zhao, Wencheng; Sun, Hongqiang; Li, Zhen-zi; Fu, Zhou

doi:10.1016/j.toxlet.2017.11.030

Cited by 41 publications

(18 citation statements)

References 37 publications

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“…Besides, calpain inhibition attenuated bleomycininduced pulmonary fibrosis via switching the development of EMT 49 . Moreover, activation of NF-κB was found to activate the expression of potent EMT inducers, like snail and zeb, suggesting a close link between fibrosis, inflammation, and EMT 50,51 . NLRP3 inflammasome activation could promote the EMT process during the fibrosis 52 .…”

Section: Discussionmentioning

confidence: 99%

Scutellarin ameliorates pulmonary fibrosis through inhibiting NF-κB/NLRP3-mediated epithelial–mesenchymal transition and inflammation

et al. 2020

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Idiopathic pulmonary fibrosis (IPF) is featured with inflammation and extensive lung remodeling caused by overloaded deposition of extracellular matrix. Scutellarin is the major effective ingredient of breviscapine and its anti-inflammation efficacy has been reported before. Nevertheless, the impact of scutellarin on IPF and the downstream molecular mechanism remain unclear. In this study, scutellarin suppressed BLM-induced inflammation via NF-κB/NLRP3 pathway both in vivo and in vitro. BLM significantly elevated p-p65/p65 ratio, IκBα degradation, and levels of NLRP3, caspase-1, caspase-11, ASC, GSDMDNterm, IL-1β, and IL-18, while scutellarin reversed the above alterations except for that of caspase-11. Scutellarin inhibited BLM-induced epithelial–mesenchymal transition (EMT) process in vivo and in vitro. The expression levels of EMT-related markers, including fibronectin, vimentin, N-cadherin, matrix metalloproteinase 2 (MMP-2) and MMP-9, were increased in BLM group, and suppressed by scutellarin. The expression level of E-cadherin showed the opposite changes. However, overexpression of NLRP3 eliminated the anti-inflammation and anti-EMT functions of scutellarin in vitro. In conclusion, scutellarin suppressed inflammation and EMT in BLM-induced pulmonary fibrosis through NF-κB/NLRP3 signaling.

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Section: Discussionmentioning

confidence: 99%

Scutellarin ameliorates pulmonary fibrosis through inhibiting NF-κB/NLRP3-mediated epithelial–mesenchymal transition and inflammation

et al. 2020

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“…Therefore, it is necessary to further study how to block the fibrotic signaling pathway and promote ECM decomposition to inhibit or reverse the process of fibrosis. TGF-β is the strongest inducer, playing an important role in EMT[ 38 ]. The Smad signaling pathway induced by TGF-β can promote the expression of ECM and inhibit the transcriptional activity of matrix degradation genes, resulting in ECM deposition in interstitial cells and leading to fibrosis[ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Total flavone of Abelmoschus manihot suppresses epithelial-mesenchymal transition via interfering transforming growth factor-β1 signaling in Crohn’s disease intestinal fibrosis

Yang¹,

Zhu²,

Li³

et al. 2018

WJG

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AIMTo explore the role and mechanism of total flavone of Abelmoschus manihot (TFA) on epithelial-mesenchymal transition (EMT) progress of Crohn’s disease (CD) intestinal fibrosis.METHODSFirst, CCK-8 assay was performed to assess TFA on the viability of intestinal epithelial (IEC-6) cells and select the optimal concentrations of TFA for our further studies. Then cell morphology, wound healing and transwell assays were performed to examine the effect of TFA on morphology, migration and invasion of IEC-6 cells treated with TGF-β1. In addition, immunofluorescence, real-time PCR analysis (qRT-PCR) and western blotting assays were carried out to detect the impact of TFA on EMT progress. Moreover, western blotting assay was performed to evaluate the function of TFA on the Smad and MAPK signaling pathways. Further, the role of co-treatment of TFA and si-Smad or MAPK inhibitors has been examined by qRT-PCR, western blotting, morphology, wound healing and transwell assays.RESULTSIn this study, TFA promoted transforming growth factor-β1 (TGF-β1)-induced (IEC-6) morphological change, migration and invasion, and increased the expression of epithelial markers and reduced the levels of mesenchymal markers, along with the inactivation of Smad and MAPK signaling pathways. Moreover, we revealed that si-Smad and MAPK inhibitors effectively attenuated TGF-β1-induced EMT in IEC-6 cells. Importantly, co-treatment of TFA and si-Smad or MAPK inhibitors had better inhibitory effects on TGF-β1-induced EMT in IEC-6 cells than either one of them.CONCLUSIONThese findings could provide new insight into the molecular mechanisms of TFA on TGF-β1-induced EMT in IEC-6 cells and TFA is expected to advance as a new therapy to treat CD intestinal fibrosis.

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“…In vitro studies suggest a synergistic effect of TGF-β1 and EGF in stimulating EMT [248]. Immunohistochemical methods have been also used to study the role of the Wnt/β-catenin signaling pathway in IPF [249]. Furthermore, the different expression levels of S100A4 in fibroblasts in several in vivo models suggest that different fibroblast cell subtypes and myofibroblasts coexist during the development of pulmonary fibrosis [248,250].…”

Section: Epithelial-mesenchymal Transition (Emt)mentioning

confidence: 99%

Emerging cellular and molecular determinants of idiopathic pulmonary fibrosis

Phan

Paliogiannis

Nasrallah

et al. 2020

Cell. Mol. Life Sci.

236

152

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Idiopathic pulmonary fibrosis (IPF), the most common form of idiopathic interstitial pneumonia, is a progressive, irreversible, and typically lethal disease characterized by an abnormal fibrotic response involving vast areas of the lungs. Given the poor knowledge of the mechanisms underpinning IPF onset and progression, a better understanding of the cellular processes and molecular pathways involved is essential for the development of effective therapies, currently lacking. Besides a number of established IPF-associated risk factors, such as cigarette smoking, environmental factors, comorbidities, and viral infections, several other processes have been linked with this devastating disease. Apoptosis, senescence, epithelial-mesenchymal transition, endothelial-mesenchymal transition, and epithelial cell migration have been shown to play a key role in IPF-associated tissue remodeling. Moreover, molecules, such as chemokines, cytokines, growth factors, adenosine, glycosaminoglycans, non-coding RNAs, and cellular processes including oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, hypoxia, and alternative polyadenylation have been linked with IPF development. Importantly, strategies targeting these processes have been investigated to modulate abnormal cellular phenotypes and maintain tissue homeostasis in the lung. This review provides an update regarding the emerging cellular and molecular mechanisms involved in the onset and progression of IPF.

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Triptolide suppresses paraquat induced idiopathic pulmonary fibrosis by inhibiting TGFB1-dependent epithelial mesenchymal transition

Cited by 41 publications

References 37 publications

Scutellarin ameliorates pulmonary fibrosis through inhibiting NF-κB/NLRP3-mediated epithelial–mesenchymal transition and inflammation

Scutellarin ameliorates pulmonary fibrosis through inhibiting NF-κB/NLRP3-mediated epithelial–mesenchymal transition and inflammation

Total flavone of Abelmoschus manihot suppresses epithelial-mesenchymal transition via interfering transforming growth factor-β1 signaling in Crohn’s disease intestinal fibrosis

Emerging cellular and molecular determinants of idiopathic pulmonary fibrosis

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