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Fluorofenidone suppresses epithelial-mesenchymal transition and the expression of connective tissue growth factor via inhibiting TGF-beta/Smads signaling in human proximal tubular epithelial cells.
Pharmazie. 2011 Dec; 66(12):961-7.P

Abstract

OBJECTIVES

The present study was designed to investigate the potential effects and mechanism of fluorofenidone (AKF-PD) on transforming growth factor beta1 (TGF-beta1)-induced tubular epithelial-mesenchymal transition (EMT) and the expression of connective tissue growth factor (CTGF) in human proximal tubular epithelial cells.

METHODS

HK-2 cells were pretreated with AKF-PD, pirfenidone (PFD), Losartan, and SB431542 (an inhibitor of TGF-beta type I receptor). The pretreated HK-2 cells were subsequently co-treated with TGF-beta1 (5 ng/ml). The morphological changes of HK-2 cells were observed under an inverted microscope. Expression of alpha-SMA was detected by Western blot and immunofluorescence. The protein expression of ZO-1, fibronectin, CTGF, phosphorylated Smad2 (p-Smad2) and phosphorylated Smad3 (p-Smad3) were evaluated by Western blot.

RESULTS

Through down-regulation of p-Smad2 and p-Smad3 proteins, AKF-PD significantly inhibited protein expression of alpha-SMA, fibronectin, and CTGF. Meanwhile, the depressed ZO-1 expression and morphological changes induced by TGF-beta1 were attenuated by AKF-PD.

CONCLUSION

AKF-PD acts as an anti-fibrotic agent through blocking TGF-beta/Smads signaling and consequently inhibits TGF-beta1-induced EMT and CTGF expression in human proximal tubular epithelial cells.

Authors+Show Affiliations

Yuan Q
Division of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan.
Wang L
No affiliation info available
Zhang F
No affiliation info available
Wang R
No affiliation info available
Fu X
No affiliation info available
Peng Z
No affiliation info available
Ning W
No affiliation info available
Hu G
No affiliation info available
Wang Z
No affiliation info available
Tao L
No affiliation info available

MeSH

Angiotensin II Type 1 Receptor BlockersBlotting, WesternCell LineConnective Tissue Growth FactorEpithelial CellsEpithelial-Mesenchymal TransitionFibronectinsFluorescent Antibody TechniqueHumansIndicators and ReagentsKidney Tubules, ProximalLosartanPyridonesSignal TransductionSmad ProteinsTransforming Growth Factor beta

Pub Type(s)

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

Language

eng

PubMed ID

22312703

Citation

Yuan, Qiongjing, et al. "Fluorofenidone Suppresses Epithelial-mesenchymal Transition and the Expression of Connective Tissue Growth Factor Via Inhibiting TGF-beta/Smads Signaling in Human Proximal Tubular Epithelial Cells." Die Pharmazie, vol. 66, no. 12, 2011, pp. 961-7.
Yuan Q, Wang L, Zhang F, et al. Fluorofenidone suppresses epithelial-mesenchymal transition and the expression of connective tissue growth factor via inhibiting TGF-beta/Smads signaling in human proximal tubular epithelial cells. Pharmazie. 2011;66(12):961-7.
Yuan, Q., Wang, L., Zhang, F., Wang, R., Fu, X., Peng, Z., Ning, W., Hu, G., Wang, Z., & Tao, L. (2011). Fluorofenidone suppresses epithelial-mesenchymal transition and the expression of connective tissue growth factor via inhibiting TGF-beta/Smads signaling in human proximal tubular epithelial cells. Die Pharmazie, 66(12), 961-7.
Yuan Q, et al. Fluorofenidone Suppresses Epithelial-mesenchymal Transition and the Expression of Connective Tissue Growth Factor Via Inhibiting TGF-beta/Smads Signaling in Human Proximal Tubular Epithelial Cells. Pharmazie. 2011;66(12):961-7. PubMed PMID: 22312703.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fluorofenidone suppresses epithelial-mesenchymal transition and the expression of connective tissue growth factor via inhibiting TGF-beta/Smads signaling in human proximal tubular epithelial cells. AU - Yuan,Qiongjing, AU - Wang,Linghao, AU - Zhang,Fangfang, AU - Wang,Rui, AU - Fu,Xiao, AU - Peng,Zhangzhe, AU - Ning,Wangbin, AU - Hu,Gaoyun, AU - Wang,Zhaohe, AU - Tao,Lijian, PY - 2012/2/9/entrez PY - 2012/2/9/pubmed PY - 2012/3/21/medline SP - 961 EP - 7 JF - Die Pharmazie JO - Pharmazie VL - 66 IS - 12 N2 - OBJECTIVES: The present study was designed to investigate the potential effects and mechanism of fluorofenidone (AKF-PD) on transforming growth factor beta1 (TGF-beta1)-induced tubular epithelial-mesenchymal transition (EMT) and the expression of connective tissue growth factor (CTGF) in human proximal tubular epithelial cells. METHODS: HK-2 cells were pretreated with AKF-PD, pirfenidone (PFD), Losartan, and SB431542 (an inhibitor of TGF-beta type I receptor). The pretreated HK-2 cells were subsequently co-treated with TGF-beta1 (5 ng/ml). The morphological changes of HK-2 cells were observed under an inverted microscope. Expression of alpha-SMA was detected by Western blot and immunofluorescence. The protein expression of ZO-1, fibronectin, CTGF, phosphorylated Smad2 (p-Smad2) and phosphorylated Smad3 (p-Smad3) were evaluated by Western blot. RESULTS: Through down-regulation of p-Smad2 and p-Smad3 proteins, AKF-PD significantly inhibited protein expression of alpha-SMA, fibronectin, and CTGF. Meanwhile, the depressed ZO-1 expression and morphological changes induced by TGF-beta1 were attenuated by AKF-PD. CONCLUSION: AKF-PD acts as an anti-fibrotic agent through blocking TGF-beta/Smads signaling and consequently inhibits TGF-beta1-induced EMT and CTGF expression in human proximal tubular epithelial cells. SN - 0031-7144 UR - https://www.unboundmedicine.com/medline/citation/22312703/Fluorofenidone_suppresses_epithelial_mesenchymal_transition_and_the_expression_of_connective_tissue_growth_factor_via_inhibiting_TGF_beta/Smads_signaling_in_human_proximal_tubular_epithelial_cells_ DB - PRIME DP - Unbound Medicine ER -