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논문분류	춘계학술대회 초록집
제목	The Farnesoid X Receptor Ligand Prevents Cisplatin-induced Renal Injury by Enhancing the Orphan Nuclear Receptor SHP
저자	Eun Hui Bae1, Hong Sang Choi1, Soo Yeon Joo2, In Jin Kim2, Chang Seong Kim1, Joon Seok Choi1, Seong Kwon Ma1, Jong Un Lee2, Soo Wan Kim1
출판정보	2013; 2013(1):
키워드	Farnesoid X receptor, Small heterodimer partner, Cisplatin
초록	The farnesoid X receptor (FXR) has been shown to be largely expressed in liver, intestine, and kidney. In the present study, we investigated whether 6-ethyl chenodeoxycholic acid (6-ECDCA or INT-747), a semisynthetic derivative of chenodeoxycholic aicd (CDCA) which is FXR ligand, protects renal injury and modulate small heterodimer partner (SHP) in human proximal tubular (HK2) cell lines and cisplatin-induced renal injury mice model. Cisplatin decreased the protein expression of SHP on HK2 cell and cisplatin-treated mice, which is improved by FXR ligand treatment. Furthermore, FXR ligand attenuated renal injury in H&E stain compared with cisplatin-treated mice. FXR ligand also attenuated the protein expression of transforming growth factor β1 (TGF-β1), Smad signaling, and the subsequent epithelial-to-mesenchymal process, inflammatory markers and cytokines, and apoptotic markers in cisplatin-treated mice. The cisplatin induce NF-κB expression in HK2 cell which is attenuated by FXR ligand pretreatment. In SHP deletion state by siRNA, the protein expression TGF-β1, p-JNK and Bax which is proapoptotic protein was not attenuated, while overexpression of SHP induce decreasing of those protein expression by FXR ligand treatment in cisplatin pretreated HK2 cells. In conclusion, FXR ligand, 6-ECDCA prevents cisplatin-inudced renal injury and its potential mechanism might be the effect of 6-ECDCA in decreasing the antifibrosis, anti-inflammation, and anti-apoptosis effects by SHP induction.
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