Farnesoid X Receptor Ligand Prevents Cisplatin-Induced Kidney Injury by Enhancing Small Heterodimer Partner

被引：35

作者：

Bae, Eun Hui ^{[1
]}

Choi, Hong Sang ^{[1
]}

Joo, Soo Yeon ^{[2
]}

Kim, In Jin ^{[2
]}

Kim, Chang Seong ^{[1
]}

Choi, Joon Seok ^{[1
]}

Ma, Seong Kwon ^{[1
]}

Lee, JongUn ^{[2
]}

Kim, Soo Wan ^{[1
]}

机构：

[1] Chonnam Natl Univ Med Sch, Dept Internal Med, Kwangju, South Korea

[2] Chonnam Natl Univ Med Sch, Dept Physiol, Kwangju, South Korea

来源：

PLOS ONE | 2014年 / 9卷 / 01期

基金：

新加坡国家研究基金会;

关键词：

RENAL INTERSTITIAL FIBROSIS; NUCLEAR RECEPTOR; TERMINAL KINASE; CELL APOPTOSIS; KAPPA-B; ACID; RATS; IDENTIFICATION; INFLAMMATION; INHIBITION;

D O I：

10.1371/journal.pone.0086553

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

The farnesoid X receptor (FXR) is mainly expressed in liver, intestine and kidney. We investigated whether 6-ethyl chenodeoxycholic acid (6ECDCA), a semisynthetic derivative of chenodeoxycholic aicd (CDCA, an FXR ligand), protects against kidney injury and modulates small heterodimer partner (SHP) in cisplatin-induced kidney injury. Cisplatin inhibited SHP protein expression in the kidney of cisplatin-treated mice and human proximal tubular (HK2) cells; this effect was counteracted by FXR ligand. Hematoxylin and eosin staining revealed the presence of tubular casts, obstructions and dilatations in cisplatin-induced kidney injury, which was attenuated by FXR ligand. FXR ligand also attenuated protein expression of transforming growth factor-beta 1 (TGF-beta 1), Smad signaling, and the epithelial-to-mesenchymal transition process, inflammatory markers and cytokines, and apoptotic markers in cisplatin-treated mice. Cisplatin induced NF-kappa B activation in HK2 cell; this effect was attenuated by pretreatment with FXR ligand. In SHP knockdown by small interfering RNA, cisplatin-induced activation of TGF-beta 1, p-JNK and Bax/Bcl-2 ratio was not attenuated, while SHP overexpression and FXR ligand inhibited expression of these proteins in cisplatin-pretreated HK2 cells. In conclusion, FXR ligand, 6ECDCA prevents cisplatin-induced kidney injury, the underlying mechanism of which may be associated with anti-fibrotic, anti-inflammatory, and anti-apoptotic effects through SHP induction.

引用

页数：12

共 30 条

[1]

c-Jun N-Terminal Kinase 1 Is Required for the Development of Pulmonary Fibrosis [J].