Klotho attenuates high glucose-induced fibronectin and cell hypertrophy via the ERK1/2-p38 kinase signaling pathway in renal interstitial fibroblasts

被引：37
|
作者：
Huang, Jau-Shyang [1 ]
Chuang, Chao-Tang [2 ]
Liu, Mei-Hsin [3 ]
Lin, Sheng-Hsuan [2 ]
Guh, Jinn-Yuh [4 ,5 ]
Chuang, Lea-Yea [3 ]
机构：
[1] Chung Hwa Univ Med Technol, Dept Biol Sci & Technol, Tainan, Taiwan
[2] Kaohsiung Med Univ, Grad Inst Med, Coll Med, Kaohsiung, Taiwan
[3] Kaohsiung Med Univ, Dept Biochem, Coll Med, Kaohsiung, Taiwan
[4] Kaohsiung Med Univ Hosp, Dept Internal Med, Kaohsiung 807, Taiwan
[5] Kaohsiung Med Univ, Dept Internal Med, Coll Med, Kaohsiung, Taiwan
来源：
MOLECULAR AND CELLULAR ENDOCRINOLOGY | 2014年 / 390卷 / 1-2期
关键词：
Klotho; Diabetic nephropathy; Renal fibrosis; Transforming growth factor-beta; Cell hypertrophy; DIABETIC-NEPHROPATHY; TGF-BETA; KIDNEY-DISEASE; NITRIC-OXIDE; EXPRESSION; RECEPTOR; ACTIVATION; FIBROSIS; MICE; CONTRIBUTES;
D O I：
10.1016/j.mce.2014.04.001
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
Although exogenous klotho attenuates renal fibrosis, it is not known if exogenous klotho attenuates diabetic nephropathy (DN). Thus, we studied the anti-fibrotic mechanisms of klotho in terms of transforming growth factor-beta (TGF-beta) and signaling pathways in high glucose (HG, 30 mM)-cultured renal interstitial fibroblast (NRK-49F) cells. We found that HG increased klotho mRNA and protein expression. HG also activated TGF-beta Smad2/3 signaling and activated extracellular signal-regulated kinase (ERK1/2) and p38 kinase signaling. Exogenous klotho (400 pM) attenuated HG-induced TGF-beta bioactivity, type II TGF-beta receptor (TGF-beta RII) protein expression and TGF-beta Smad2/3 signaling. Klotho also attenuated HG-activated ERK1/2 and p38 kinase. Additionally, klotho and inhibitors of ERK1/2 or p38 kinase attenuated HG-induced fibronectin and cell hypertrophy. Finally, renal tubular expression of klotho decreased in the streptozotin-diabetic rats at 8 weeks. Thus, exogenous klotho attenuates HG-induced profibrotic genes, TGF-beta signaling and cell hypertrophy in NRK-49F cells. Moreover, klotho attenuates HG-induced fibronectin expression and cell hypertrophy via the ERK1/2 and p38 kinase-dependent pathways. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码：45 / 53
页数：9
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