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Fluorofenidone attenuates tubulointerstitial fibrosis by inhibiting TGF-β(1)-induced fibroblast activation.
Am J Nephrol. 2011; 34(2):181-94.AJ

Abstract

BACKGROUND

Novel therapeutic agents are urgently needed to combat renal fibrosis. The purpose of this study was to assess, using complete unilateral ureteral obstruction (UUO) in rats, whether fluorofenidone (AKF-PD) [1-(3-fluorophenyl)-5-methyl-2-(1H)-pyridone] inhibits renal fibrosis, and to determine whether it exerts its inhibitory function on renal fibroblast activation.

METHODS

Sprague-Dawley rats were randomly divided into 3 groups: sham operation, UUO and UUO/AKF-PD (500 mg/kg/day). Renal function, tubulointerstitium damage index score, extracellular matrix (ECM) deposition, and the expressions of TGF-β(1), collagen III, α-SMA, p-Smad2, p-Smad3, p-ERK1/2, p-JNK and p-p38 were measured. In addition, the expressions of α-SMA, fibronectin, CTGF, p-Smad2/3, p-ERK1/2, p-p38 and p-JNK were measured in TGF-β(1)-stimulated normal rat renal fibroblasts (NRK-49F).

RESULTS

AKF-PD treatment significantly attenuated tubulointerstitium damage, ECM deposition, the expressions of TGF-β(1), collagen III, α-SMA, p-ERK1/2, p-p38 and p-JNK in vivo. In vitro, AKF-PD dose-dependently inhibited expressions of α-SMA, fibronectin and CTGF. Furthermore, AKF-PD did not inhibit Smad2/3 phosphorylation or nuclear accumulation, but rather attenuated ERK, p38 and JNK activation.

CONCLUSION

AKF-PD treatment inhibits the progression of renal interstitial fibrosis in obstructed kidneys; this is potentially achieved by suppressing fibroblast activation. Therefore, AKF-PD is a special candidate for the treatment of renal fibrosis.

Authors+Show Affiliations

Division of Nephrology, Xiangya Hospital, Central South University, Changsha, China.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 availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

21791914

Citation

Yuan, Qiongjing, et al. "Fluorofenidone Attenuates Tubulointerstitial Fibrosis By Inhibiting TGF-β(1)-induced Fibroblast Activation." American Journal of Nephrology, vol. 34, no. 2, 2011, pp. 181-94.
Yuan Q, Wang R, Peng Y, et al. Fluorofenidone attenuates tubulointerstitial fibrosis by inhibiting TGF-β(1)-induced fibroblast activation. Am J Nephrol. 2011;34(2):181-94.
Yuan, Q., Wang, R., Peng, Y., Fu, X., Wang, W., Wang, L., Zhang, F., Peng, Z., Ning, W., Hu, G., Wang, Z., & Tao, L. (2011). Fluorofenidone attenuates tubulointerstitial fibrosis by inhibiting TGF-β(1)-induced fibroblast activation. American Journal of Nephrology, 34(2), 181-94. https://doi.org/10.1159/000329080
Yuan Q, et al. Fluorofenidone Attenuates Tubulointerstitial Fibrosis By Inhibiting TGF-β(1)-induced Fibroblast Activation. Am J Nephrol. 2011;34(2):181-94. PubMed PMID: 21791914.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fluorofenidone attenuates tubulointerstitial fibrosis by inhibiting TGF-β(1)-induced fibroblast activation. AU - Yuan,Qiongjing, AU - Wang,Rui, AU - Peng,Yu, AU - Fu,Xiao, AU - Wang,Wei, AU - Wang,Linghao, AU - Zhang,Fangfang, AU - Peng,Zhangzhe, AU - Ning,Wangbin, AU - Hu,Gaoyun, AU - Wang,Zhaohe, AU - Tao,Lijian, Y1 - 2011/07/23/ PY - 2011/03/07/received PY - 2011/04/30/accepted PY - 2011/7/28/entrez PY - 2011/7/28/pubmed PY - 2012/1/19/medline SP - 181 EP - 94 JF - American journal of nephrology JO - Am J Nephrol VL - 34 IS - 2 N2 - BACKGROUND: Novel therapeutic agents are urgently needed to combat renal fibrosis. The purpose of this study was to assess, using complete unilateral ureteral obstruction (UUO) in rats, whether fluorofenidone (AKF-PD) [1-(3-fluorophenyl)-5-methyl-2-(1H)-pyridone] inhibits renal fibrosis, and to determine whether it exerts its inhibitory function on renal fibroblast activation. METHODS: Sprague-Dawley rats were randomly divided into 3 groups: sham operation, UUO and UUO/AKF-PD (500 mg/kg/day). Renal function, tubulointerstitium damage index score, extracellular matrix (ECM) deposition, and the expressions of TGF-β(1), collagen III, α-SMA, p-Smad2, p-Smad3, p-ERK1/2, p-JNK and p-p38 were measured. In addition, the expressions of α-SMA, fibronectin, CTGF, p-Smad2/3, p-ERK1/2, p-p38 and p-JNK were measured in TGF-β(1)-stimulated normal rat renal fibroblasts (NRK-49F). RESULTS: AKF-PD treatment significantly attenuated tubulointerstitium damage, ECM deposition, the expressions of TGF-β(1), collagen III, α-SMA, p-ERK1/2, p-p38 and p-JNK in vivo. In vitro, AKF-PD dose-dependently inhibited expressions of α-SMA, fibronectin and CTGF. Furthermore, AKF-PD did not inhibit Smad2/3 phosphorylation or nuclear accumulation, but rather attenuated ERK, p38 and JNK activation. CONCLUSION: AKF-PD treatment inhibits the progression of renal interstitial fibrosis in obstructed kidneys; this is potentially achieved by suppressing fibroblast activation. Therefore, AKF-PD is a special candidate for the treatment of renal fibrosis. SN - 1421-9670 UR - https://www.unboundmedicine.com/medline/citation/21791914/Fluorofenidone_attenuates_tubulointerstitial_fibrosis_by_inhibiting_TGF_β_1__induced_fibroblast_activation_ L2 - https://www.karger.com?DOI=10.1159/000329080 DB - PRIME DP - Unbound Medicine ER -