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Arctigenin suppresses transforming growth factor-β1-induced expression of monocyte chemoattractant protein-1 and the subsequent epithelial-mesenchymal transition through reactive oxygen species-dependent ERK/NF-κB signaling pathway in renal tubular epithelial cells.
Free Radic Res. 2015; 49(9):1095-113.FR

Abstract

Transforming growth factor-β1 (TGF-β1) induces expression of the proinflammatory and profibrotic cytokine monocyte chemoattractant protein-1 (MCP-1) in tubular epithelial cells (TECs) and thereby contributes to the tubular epithelial-mesenchymal transition (EMT), which in turn leads to the progression of tubulointerstitial inflammation into tubulointerstitial fibrosis. Exactly how TGF-β1 causes MCP-1 overexpression and subsequent EMT is not well understood. Using human tubular epithelial cultures, we found that TGF-β1 upregulated the expression of reduced nicotinamide adenine dinucleotide phosphate oxidases 2 and 4 and their regulatory subunits, inducing the production of reactive oxygen species. These reactive species activated a signaling pathway mediated by extracellular signal-regulated kinase (ERK1/2) and nuclear factor-κB (NF-κB), which upregulated expression of MCP-1. Incubating cultures with TGF-β1 was sufficient to induce hallmarks of EMT, such as downregulation of epithelial marker proteins (E-cadherin and zonula occludens-1), induction of mesenchymal marker proteins (α-smooth muscle actin, fibronectin, and vimentin), and elevated cell migration and invasion in an EMT-like manner. Overexpressing MCP-1 in cells exposed to TGF-β1 exacerbated these EMT-like changes. Pretreating cells with the antioxidant and anti-inflammatory compound arctigenin (ATG) protected them against these TGF-β1-induced EMT-like changes; the compound worked by inhibiting the ROS/ERK1/2/NF-κB pathway to decrease MCP-1 upregulation. These findings suggest ATG as a new therapeutic candidate to inhibit or even reverse tubular EMT-like changes during progression to tubulointerstitial fibrosis, and they provide the first clues to how ATG may work.

Authors+Show Affiliations

Department of Pharmacology and Pharmaceutical Sciences, College of Pharmacy and Bioengineering, Chongqing University of Technology , Chongqing , P. R. China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25968940

Citation

Li, A, et al. "Arctigenin Suppresses Transforming Growth Factor-β1-induced Expression of Monocyte Chemoattractant Protein-1 and the Subsequent Epithelial-mesenchymal Transition Through Reactive Oxygen Species-dependent ERK/NF-κB Signaling Pathway in Renal Tubular Epithelial Cells." Free Radical Research, vol. 49, no. 9, 2015, pp. 1095-113.
Li A, Wang J, Zhu D, et al. Arctigenin suppresses transforming growth factor-β1-induced expression of monocyte chemoattractant protein-1 and the subsequent epithelial-mesenchymal transition through reactive oxygen species-dependent ERK/NF-κB signaling pathway in renal tubular epithelial cells. Free Radic Res. 2015;49(9):1095-113.
Li, A., Wang, J., Zhu, D., Zhang, X., Pan, R., & Wang, R. (2015). Arctigenin suppresses transforming growth factor-β1-induced expression of monocyte chemoattractant protein-1 and the subsequent epithelial-mesenchymal transition through reactive oxygen species-dependent ERK/NF-κB signaling pathway in renal tubular epithelial cells. Free Radical Research, 49(9), 1095-113. https://doi.org/10.3109/10715762.2015.1038258
Li A, et al. Arctigenin Suppresses Transforming Growth Factor-β1-induced Expression of Monocyte Chemoattractant Protein-1 and the Subsequent Epithelial-mesenchymal Transition Through Reactive Oxygen Species-dependent ERK/NF-κB Signaling Pathway in Renal Tubular Epithelial Cells. Free Radic Res. 2015;49(9):1095-113. PubMed PMID: 25968940.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Arctigenin suppresses transforming growth factor-β1-induced expression of monocyte chemoattractant protein-1 and the subsequent epithelial-mesenchymal transition through reactive oxygen species-dependent ERK/NF-κB signaling pathway in renal tubular epithelial cells. AU - Li,A, AU - Wang,J, AU - Zhu,D, AU - Zhang,X, AU - Pan,R, AU - Wang,R, Y1 - 2015/05/13/ PY - 2015/5/14/entrez PY - 2015/5/15/pubmed PY - 2016/5/25/medline KW - NADPH oxidase KW - antioxidant capacity KW - hydrogen peroxide KW - redox signaling KW - redox-sensitive transcription factors SP - 1095 EP - 113 JF - Free radical research JO - Free Radic Res VL - 49 IS - 9 N2 - Transforming growth factor-β1 (TGF-β1) induces expression of the proinflammatory and profibrotic cytokine monocyte chemoattractant protein-1 (MCP-1) in tubular epithelial cells (TECs) and thereby contributes to the tubular epithelial-mesenchymal transition (EMT), which in turn leads to the progression of tubulointerstitial inflammation into tubulointerstitial fibrosis. Exactly how TGF-β1 causes MCP-1 overexpression and subsequent EMT is not well understood. Using human tubular epithelial cultures, we found that TGF-β1 upregulated the expression of reduced nicotinamide adenine dinucleotide phosphate oxidases 2 and 4 and their regulatory subunits, inducing the production of reactive oxygen species. These reactive species activated a signaling pathway mediated by extracellular signal-regulated kinase (ERK1/2) and nuclear factor-κB (NF-κB), which upregulated expression of MCP-1. Incubating cultures with TGF-β1 was sufficient to induce hallmarks of EMT, such as downregulation of epithelial marker proteins (E-cadherin and zonula occludens-1), induction of mesenchymal marker proteins (α-smooth muscle actin, fibronectin, and vimentin), and elevated cell migration and invasion in an EMT-like manner. Overexpressing MCP-1 in cells exposed to TGF-β1 exacerbated these EMT-like changes. Pretreating cells with the antioxidant and anti-inflammatory compound arctigenin (ATG) protected them against these TGF-β1-induced EMT-like changes; the compound worked by inhibiting the ROS/ERK1/2/NF-κB pathway to decrease MCP-1 upregulation. These findings suggest ATG as a new therapeutic candidate to inhibit or even reverse tubular EMT-like changes during progression to tubulointerstitial fibrosis, and they provide the first clues to how ATG may work. SN - 1029-2470 UR - https://www.unboundmedicine.com/medline/citation/25968940/Arctigenin_suppresses_transforming_growth_factor_β1_induced_expression_of_monocyte_chemoattractant_protein_1_and_the_subsequent_epithelial_mesenchymal_transition_through_reactive_oxygen_species_dependent_ERK/NF_κB_signaling_pathway_in_renal_tubular_epithelial_cells_ L2 - https://www.tandfonline.com/doi/full/10.3109/10715762.2015.1038258 DB - PRIME DP - Unbound Medicine ER -