title: Effects of exendin-4 on the intrarenal renin-angiotensin system and interstitial fibrosis in unilateral ureteral obstruction mice: Exendin-4 and unilateral ureteral obstruction.
abstract: OBJECTIVE
  The objective of this article is to investigate the renoprotecive effects of exendin-4 in a mouse model of unilateral ureteral obstruction (UUO) and explore the putative mechanisms.
  
  
  METHODS
  Male Balbc mice underwent sham operation or UUO surgery, and then received intraperitoneal injection of vehicle or exendin-4, respectively. After 14 days, mice were sacrificed and the left kidneys were collected and analyzed by histology, immunohistochemistry, Western blot, quantitative real-time reverse transcription polymerase chain reaction, radioimmunoassay and enzyme-linked immunosorbent assay.
  
  
  RESULTS
  As compared to the sham group, mice that underwent UUO surgery developed more severe tubular injury and interstitial fibrosis, as well as higher expression of fibronectin (FN), collagen-1 (Col-1) and α-smooth muscle actin (α-SMA). Also, we observed higher expression of angiotensin-converting enzyme (ACE) while lower expression of angiotensin-converting enzyme 2 (ACE2), higher levels of intrarenal angiotensin II (Ang II) while lower levels of intrarenal angiotensin-(1-7), and higher expression of transforming growth factor β1 (TGF-β1) and phosphorylation of Smad3 (p-Smad3) in the obstructed kidneys. Impressively, these pathologic changes were significantly attenuated in the mice group of UUO treated with exendin-4.
  
  
  CONCLUSIONS
  Our present study indicates for the first time that exendin-4 exerts renoprotective effects in an experimental model of UUO, partly through regulating the balance of the intrarenal renin-angiotensin system and then inhibiting the Ang II-mediated TGF-β1/Smad3 signaling pathway.
authors.affiliation: Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Le
authors.affiliation: Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, China.
authors.forename: Zongji
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, China.
authors.forename: Junyu
authors.initials: J
authors.lastname: Xue
authors.affiliation: Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, China.
authors.forename: Mengling
authors.initials: M
authors.lastname: Cheng
authors.affiliation: Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, China.
authors.forename: Meiping
authors.initials: M
authors.lastname: Guan
authors.affiliation: Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, China xueyaoming999@126.com.
authors.forename: Yaoming
authors.initials: Y
authors.lastname: Xue
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000077270:Exenatide; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005355:Fibrosis; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D051900:Smad3 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014517:Ureteral Obstruction / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D014688:Venoms / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: C558396:Acta2 protein, mouse; D000199:Actins; D024042:Collagen Type I; D005353:Fibronectins; D010446:Peptide Fragments; D010455:Peptides; D012333:RNA, Messenger; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; D014688:Venoms; D000804:Angiotensin II; D000803:Angiotensin I; D000077270:Exenatide; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7)
keywords: Angiotensin-converting enzyme; TGF-β1/Smad3; angiotensin II; angiotensin-converting enzyme 2; exendin-4; intrarenal renin-angiotensin system; unilateral ureteral obstruction