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Mefunidone attenuates tubulointerstitial fibrosis in a rat model of unilateral ureteral obstruction.
PLoS One. 2015; 10(6):e0129283.Plos

Abstract

BACKGROUND

Inflammation has a crucial role in renal interstitial fibrosis, which is the common pathway of chronic kidney diseases. Mefunidone (MFD) is a new compound which could effectively inhibit the proliferation of renal fibroblasts in vitro. However, the overall effect of Mefunidone in renal fibrosis remains unknown.

METHODS

Sprague-Dawley rats were randomly divided intro 6 groups: sham operation, unilateral ureteral obstruction (UUO), UUO/Mefunidone (25, 50, 100mg/kg/day) and UUO/PFD (500mg/kg/day). The rats were sacrificed respectively on days 3, 7, and 14 after the operation. Tubulointerstitial injury index, interstitial collagen deposition, expression of fibronectin (FN), α-smooth muscle actin (α-SMA), type I and III collagen and the number of CD3+ and CD68+ cells were determined. The expressions of proinflammatory cytokines, p-ERK, p-IκB, and p-STAT3 were measured in human renal proximal tubular epithelial cells of HK-2 or macrophages.

RESULTS

Mefunidone treatment significantly attenuated tubulointerstitial injury, interstitial collagen deposition, expression of FN, α-SMA, type I and III collagen in the obstructive kidneys, which correlated with significantly reduced the number of T cells and macrophages in the obstructive kidneys. Mechanistically, Mefunidone significantly inhibited tumor necrosis factor-α (TNF-α-) or lipopolysaccharide (LPS)-induced production of proinflammatory cytokines. This effect is possibly due to the inhibition of phosphorylation of ERK, IκB, and STAT3.

CONCLUSION

Mefunidone treatment attenuated tubulointerstitial fibrosis in a rat model of UUO, at least in part, through inhibition of inflammation.

Authors+Show Affiliations

Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Department of Pathology, Hunan University of Chinese Medicine, Changsha, Hunan, China.Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan, China.Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan, China.Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan, China.Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan, China.Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan, China.Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan, China.Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan, China.Department of Respiration, Xiangya Hospital, Central South University, Changsha, Hunan, China.Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan, China.Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan, China.Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.Department of Medical Chemistry, School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, China.Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan, China; State Key Laboratory of Medical Genetics of China, Central South University, Changsha, Hunan, China.

Pub Type(s)

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

Language

eng

PubMed ID

26042668

Citation

Liu, Chunyan, et al. "Mefunidone Attenuates Tubulointerstitial Fibrosis in a Rat Model of Unilateral Ureteral Obstruction." PloS One, vol. 10, no. 6, 2015, pp. e0129283.
Liu C, Mei W, Tang J, et al. Mefunidone attenuates tubulointerstitial fibrosis in a rat model of unilateral ureteral obstruction. PLoS One. 2015;10(6):e0129283.
Liu, C., Mei, W., Tang, J., Yuan, Q., Huang, L., Lu, M., Wu, L., Peng, Z., Meng, J., Yang, H., Shen, H., Lv, B., Hu, G., & Tao, L. (2015). Mefunidone attenuates tubulointerstitial fibrosis in a rat model of unilateral ureteral obstruction. PloS One, 10(6), e0129283. https://doi.org/10.1371/journal.pone.0129283
Liu C, et al. Mefunidone Attenuates Tubulointerstitial Fibrosis in a Rat Model of Unilateral Ureteral Obstruction. PLoS One. 2015;10(6):e0129283. PubMed PMID: 26042668.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mefunidone attenuates tubulointerstitial fibrosis in a rat model of unilateral ureteral obstruction. AU - Liu,Chunyan, AU - Mei,Wenjuan, AU - Tang,Juan, AU - Yuan,Qiongjing, AU - Huang,Ling, AU - Lu,Miaomiao, AU - Wu,Lin, AU - Peng,Zhangzhe, AU - Meng,Jie, AU - Yang,Huixiang, AU - Shen,Hong, AU - Lv,Ben, AU - Hu,Gaoyun, AU - Tao,Lijian, Y1 - 2015/06/04/ PY - 2014/12/30/received PY - 2015/05/06/accepted PY - 2015/6/5/entrez PY - 2015/6/5/pubmed PY - 2016/5/11/medline SP - e0129283 EP - e0129283 JF - PloS one JO - PLoS One VL - 10 IS - 6 N2 - BACKGROUND: Inflammation has a crucial role in renal interstitial fibrosis, which is the common pathway of chronic kidney diseases. Mefunidone (MFD) is a new compound which could effectively inhibit the proliferation of renal fibroblasts in vitro. However, the overall effect of Mefunidone in renal fibrosis remains unknown. METHODS: Sprague-Dawley rats were randomly divided intro 6 groups: sham operation, unilateral ureteral obstruction (UUO), UUO/Mefunidone (25, 50, 100mg/kg/day) and UUO/PFD (500mg/kg/day). The rats were sacrificed respectively on days 3, 7, and 14 after the operation. Tubulointerstitial injury index, interstitial collagen deposition, expression of fibronectin (FN), α-smooth muscle actin (α-SMA), type I and III collagen and the number of CD3+ and CD68+ cells were determined. The expressions of proinflammatory cytokines, p-ERK, p-IκB, and p-STAT3 were measured in human renal proximal tubular epithelial cells of HK-2 or macrophages. RESULTS: Mefunidone treatment significantly attenuated tubulointerstitial injury, interstitial collagen deposition, expression of FN, α-SMA, type I and III collagen in the obstructive kidneys, which correlated with significantly reduced the number of T cells and macrophages in the obstructive kidneys. Mechanistically, Mefunidone significantly inhibited tumor necrosis factor-α (TNF-α-) or lipopolysaccharide (LPS)-induced production of proinflammatory cytokines. This effect is possibly due to the inhibition of phosphorylation of ERK, IκB, and STAT3. CONCLUSION: Mefunidone treatment attenuated tubulointerstitial fibrosis in a rat model of UUO, at least in part, through inhibition of inflammation. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/26042668/Mefunidone_attenuates_tubulointerstitial_fibrosis_in_a_rat_model_of_unilateral_ureteral_obstruction_ L2 - https://dx.plos.org/10.1371/journal.pone.0129283 DB - PRIME DP - Unbound Medicine ER -