title: [Valsartan inhibits angiotensin II-Notch signaling of mesangial cells induced by high glucose].
abstract: OBJECTIVE
  To explore the role of angiotensin II (Ang II)-Notch signaling in high glucose-induced secretion of extracellular matrix of rat mesangial cells (RMCs) and to further investigate the protective effect of valsartan (one of Ang II receptor blockers) on kidney.
  
  
  METHODS
  Subcultured RMCs were divided into groups as follows: normal glucose group (5.5 mmol/L glucose); high glucose group (30 mmol/L glucose); high concentration of mannitol as osmotic control group (5.5 mmol/L glucose and 24.5 mmol/L mannitol); normal glucose plus 1 μmol/L N-[N-(3, 5-difluorophenacetyl)-L-alanyl ]-S-phenylglycine t-butyl ester (DAPT) group; normal glucose plus (1, 5, 10) μmol/L valsartan group; high glucose plus 1 μmol/L DAPT group; high glucose plus (1, 5, 10) μmol/L valsartan group. Cells and supernatants were harvested after 12, 24 and 48 hours. Notch1 expression was examined by Western blotting. Secretion of transforming growth factor (TGF-β) and fibronectin (FN) were detected by ELISA.
  
  
  RESULTS
  Compared to the normal glucose group, Notch1 expression was elevated in the high glucose group after 12 hours, and peaked at 24 hours. Besides, secretion of TGF-β and FN were much higher in the high glucose group than in the normal glucose group in a time-dependent manner. Compared to the untreated group, Notch1 expression decreased in a dose-dependent manner in the valsartan or DAPT treated group under high glucose after 24 hours. After pre-treatment by either valsartan or DAPT in the high glucose group, secretion of TGF-β and FN obviously decreased as compared to the untreated group.
  
  
  CONCLUSIONS
  Hyperglycemia could stimulate activation of Notch signaling in cultured RMCs, which may increase secretion of downstream fibrotic factors such as TGF-β and FN. Valsartan may decrease the secretion of downstream FN in a dose-dependent manner via inhibiting AngII-Notch signaling.
authors.affiliation: Department of Endocrinology, First Affiliated Hospital, China Medical University, Shenyang 110001, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Department of Endocrinology, First Affiliated Hospital, China Medical University, Shenyang 110001, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Lyu
authors.affiliation: Department of Endocrinology, First Affiliated Hospital, China Medical University, Shenyang 110001, China.
authors.forename: Can
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Endocrinology, First Affiliated Hospital, China Medical University, Shenyang 110001, China.
authors.forename: Sha
authors.initials: S
authors.lastname: Lei
authors.affiliation: Department of Endocrinology, First Affiliated Hospital, China Medical University, Shenyang 110001, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Department of Endocrinology, First Affiliated Hospital, China Medical University, Shenyang 110001, China. *Corresponding author, E-mail: wqycmu@163.com.
authors.forename: Qiuyue
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004151:Dipeptides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005353:Fibronectins / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D051881:Receptor, Notch1 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D000068756:Valsartan / Q000494:pharmacology*
chemical_list: D004151:Dipeptides; D005353:Fibronectins; C419410:N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester; D051881:Receptor, Notch1; D016212:Transforming Growth Factor beta; D000804:Angiotensin II; D000068756:Valsartan; D005947:Glucose