title: Artesunate attenuates unilateral ureteral obstruction-induced renal fibrosis by regulating the expressions of bone morphogenetic protein-7 and uterine sensitization-associated gene-1 in rats.
abstract: OBJECTIVE
  Kidney fibrosis is the most common final stage of progressive renal disease. Bone morphogenetic protein-7 (BMP-7) has been shown to be important in both preservation of kidney function and resistance to injury. Recently, it has been realized that uterine sensitization-associated gene-1 (USAG-1) functions as a kidney-specific BMP antagonist. Because of the reported anti-fibrotic effects of artesunate (Art), this study was designed to investigate the effects of Art on renal fibrosis in unilateral ureteral obstruction (UUO) rats and to explore the underlying mechanisms.
  
  
  METHODS
  Thirty male Sprague-Dawley rats were randomly divided into five groups: Sham group, UUO group, low-dose Art-treated (Art-L), middle-dose Art-treated (Art-M), and high-dose Art-treated (Art-H) groups. The UUO rat model was established by ligating the left ureter. Fourteen days later, interstitial collagen deposition, expression of USAG-1, BMP-7, E-cadherin, α-smooth muscle actin (α-SMA), fibronectin (FN), collagen I, as well as the inflammatory infiltration levels in the kidneys were assessed.
  
  
  RESULTS
  Art treatment significantly attenuated the deposition of interstitial collagens in the UUO rats' kidneys and exhibited the ability to improve renal function, followed by the up-regulated expression of BMP-7 and E-cadherin and the down-regulated expression of USAG-1 and α-SMA. In addition, increased macrophages infiltration in the kidneys of the UUO rats were also attenuated by the administration of Art.
  
  
  CONCLUSIONS
  These results indicate that Art is able to improve the renal function decline and renal fibrosis induced by UUO, which may be associated with the up-regulation of BMP-7 and down-regulation of USAG-1. Accordingly, Art may become a potential preventive or therapeutic agent for chronic kidney diseases.
authors: Key Laboratory of Brain Diseases Bioinformation, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, 221004, Jiangsu, China.|Department of Postgraduate Academy, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors: Jing
authors: J
authors: Cao
authors: Department of Postgraduate Academy, Xuzhou Medical College, Xuzhou, Jiangsu, China.|Department of Pharmacy, Xiangtan Central Hospital, Xiangtan, Hunan, China.
authors: Wei
authors: W
authors: Wang
authors: Department of Gastrointestinal Surgery, Xuzhou Central Hospital, Xuzhou, Jiangsu, China.
authors: Yong
authors: Y
authors: Li
authors: Department of Postgraduate Academy, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors: Jieyun
authors: J
authors: Xia
authors: Key Laboratory of Brain Diseases Bioinformation, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, 221004, Jiangsu, China.|Department of Postgraduate Academy, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors: Yingxian
authors: Y
authors: Peng
authors: Key Laboratory of Brain Diseases Bioinformation, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, 221004, Jiangsu, China.|Department of Postgraduate Academy, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors: Yaqian
authors: Y
authors: Zhang
authors: Key Laboratory of Brain Diseases Bioinformation, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, 221004, Jiangsu, China. xaz2008190@sina.com.
authors: Anzhou
authors: A
authors: Xia
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D055419:Bone Morphogenetic Protein 7 / Q000096:biosynthesis / Q000235:genetics*; D004195:Disease Models, Animal; D005355:Fibrosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D007668:Kidney / Q000473:pathology*; D007674:Kidney Diseases / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D008297:Male; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012313:RNA / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014517:Ureteral Obstruction / Q000150:complications* / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D037621:Artemisinins; D055419:Bone Morphogenetic Protein 7; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C480733:SOSTDC1 protein, human; D000077332:Artesunate; D012313:RNA
keywords: Artesunate; Bone morphogenetic protein-7; Renal fibrosis; Unilateral ureteral obstruction; Uterine sensitization-associated gene-1