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Dioscorea alata attenuates renal interstitial cellular fibrosis by regulating Smad- and epithelial-mesenchymal transition signaling pathways.
PLoS One. 2012; 7(11):e47482.Plos

Abstract

Renal interstitial fibrosis is characterized by increased extracellular matrix (ECM) synthesis. Epithelial-mesenchymal transition (EMT) in kidneys is driven by regulated expression of fibrogenic cytokines such as transforming growth factor-beta (TGF-β). Yam, or Dioscorea alata (DA) is an important herb in Chinese medicine widely used for the treatment of clinical diabetes mellitus. However, the fibrosis regulatory effect of DA is unclear. Thus, we examined TGF-β signaling mechanisms against EMT in rat fibroblast cells (NRK-49F). The characterization of DA water-extracts used various methods; after inducing cellular fibrosis in NRK-49F cells by treatment with β-hydroxybutyrate (β-HB) (10 mM), we used Western blotting to examine the protein expression in the TGF-β-related signal protein type I and type II TGF-β receptors, Smads2 and Smad3 (Smad2/3), pSmad2 and Smad3 (pSmad2/3), Smads4, Smads7, and EMT markers. These markers included E-cadherin, alpha-smooth muscle actin (α-SMA), and matrix metalloproteinase-2 (MMP-2). Bioactive TGF-β and fibronectin levels in the culture media were determined using ELISA. Expressions of fibronectin and Snail transcription factor, an EMT-regulatory transcription factor, were assessed by immunofluorescence staining. DA extract dose-dependently (50-200 µg/mL) suppressed β-HB-induced expression of fibronectin in NRK-49F cells concomitantly with the inhibition of Smad2/3, pSmad2/3, and Smad4. By contrast, Smad7 expression was significantly increased. DA extract caused a decrease in α-SMA (α-smooth muscle actin) and MMP-2 levels, and an increase in E-cadherin expression. We propose that DA extract might act as a novel fibrosis antagonist, which acts partly by down regulating the TGF-β/smad signaling pathway and modulating EMT expression.

Authors+Show Affiliations

Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

23144821

Citation

Liu, Shu-Fen, et al. "Dioscorea Alata Attenuates Renal Interstitial Cellular Fibrosis By Regulating Smad- and Epithelial-mesenchymal Transition Signaling Pathways." PloS One, vol. 7, no. 11, 2012, pp. e47482.
Liu SF, Chang SY, Lee TC, et al. Dioscorea alata attenuates renal interstitial cellular fibrosis by regulating Smad- and epithelial-mesenchymal transition signaling pathways. PLoS One. 2012;7(11):e47482.
Liu, S. F., Chang, S. Y., Lee, T. C., Chuang, L. Y., Guh, J. Y., Hung, C. Y., Hung, T. J., Hung, Y. J., Chen, P. Y., Hsieh, P. F., & Yang, Y. L. (2012). Dioscorea alata attenuates renal interstitial cellular fibrosis by regulating Smad- and epithelial-mesenchymal transition signaling pathways. PloS One, 7(11), e47482. https://doi.org/10.1371/journal.pone.0047482
Liu SF, et al. Dioscorea Alata Attenuates Renal Interstitial Cellular Fibrosis By Regulating Smad- and Epithelial-mesenchymal Transition Signaling Pathways. PLoS One. 2012;7(11):e47482. PubMed PMID: 23144821.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dioscorea alata attenuates renal interstitial cellular fibrosis by regulating Smad- and epithelial-mesenchymal transition signaling pathways. AU - Liu,Shu-Fen, AU - Chang,Shan-Yu, AU - Lee,Tao-Chen, AU - Chuang,Lea-Yea, AU - Guh,Jinn-Yuh, AU - Hung,Chien-Ya, AU - Hung,Tsung-Jen, AU - Hung,Yu-Ju, AU - Chen,Po-Yi, AU - Hsieh,Pei-fang, AU - Yang,Yu-Lin, Y1 - 2012/11/08/ PY - 2012/03/16/received PY - 2012/09/17/accepted PY - 2012/11/13/entrez PY - 2012/11/13/pubmed PY - 2013/4/23/medline SP - e47482 EP - e47482 JF - PloS one JO - PLoS One VL - 7 IS - 11 N2 - Renal interstitial fibrosis is characterized by increased extracellular matrix (ECM) synthesis. Epithelial-mesenchymal transition (EMT) in kidneys is driven by regulated expression of fibrogenic cytokines such as transforming growth factor-beta (TGF-β). Yam, or Dioscorea alata (DA) is an important herb in Chinese medicine widely used for the treatment of clinical diabetes mellitus. However, the fibrosis regulatory effect of DA is unclear. Thus, we examined TGF-β signaling mechanisms against EMT in rat fibroblast cells (NRK-49F). The characterization of DA water-extracts used various methods; after inducing cellular fibrosis in NRK-49F cells by treatment with β-hydroxybutyrate (β-HB) (10 mM), we used Western blotting to examine the protein expression in the TGF-β-related signal protein type I and type II TGF-β receptors, Smads2 and Smad3 (Smad2/3), pSmad2 and Smad3 (pSmad2/3), Smads4, Smads7, and EMT markers. These markers included E-cadherin, alpha-smooth muscle actin (α-SMA), and matrix metalloproteinase-2 (MMP-2). Bioactive TGF-β and fibronectin levels in the culture media were determined using ELISA. Expressions of fibronectin and Snail transcription factor, an EMT-regulatory transcription factor, were assessed by immunofluorescence staining. DA extract dose-dependently (50-200 µg/mL) suppressed β-HB-induced expression of fibronectin in NRK-49F cells concomitantly with the inhibition of Smad2/3, pSmad2/3, and Smad4. By contrast, Smad7 expression was significantly increased. DA extract caused a decrease in α-SMA (α-smooth muscle actin) and MMP-2 levels, and an increase in E-cadherin expression. We propose that DA extract might act as a novel fibrosis antagonist, which acts partly by down regulating the TGF-β/smad signaling pathway and modulating EMT expression. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/23144821/Dioscorea_alata_attenuates_renal_interstitial_cellular_fibrosis_by_regulating_Smad__and_epithelial_mesenchymal_transition_signaling_pathways_ L2 - https://dx.plos.org/10.1371/journal.pone.0047482 DB - PRIME DP - Unbound Medicine ER -