title: Effects of high glucose on AVP-induced hyperplasia, hypertrophy, and type IV collagen synthesis in cultured rat mesangial cells.
abstract: BACKGROUND
  Hyperglycemia is a principal characteristic of diabetes and influences many cellular functions. Diabetic nephropathy is characterized by glomerular mesangial expansion which could result from increased mesangial cell extracellular matrix synthesis induced by hyperglycemia.
  
  
  METHODS
  To investigate whether the physiological functions of mesangial cells are altered in a diabetic environment, we evaluated the effect of high extracellular glucose concentration on thymidine/leucine incorporation, hyperplasia/hypertrophy, and type IV collagen synthesis, induced by vasopressin (AVP), in cultured rat mesangial cells.
  
  
  RESULTS
  The exposure of mesangial cells to a high glucose concentration (30 mM) significantly reduced AVP-induced thymidine incorporation and hyperplasia compared with normal glucose (10 mM). By contrast, treatment of mesangial cells with AVP in the presence of high extracellular glucose significantly increased leucine incorporation, hypertrophy, and type IV collagen synthesis compared with those at normal glucose levels. The administration of staurosporine, a protein kinase C inhibitor, reversed these effects of high-glucose conditions. Furthermore, the nonpeptide AVP V(1A) receptor-selective antagonists potently inhibited these AVP-induced physiological responses in mesangial cells cultured in high-glucose conditions.
  
  
  CONCLUSIONS
  These results demonstrate that high glucose suppresses mesangial cell proliferation but enhances hypertrophy and type IV collagen synthesis induced by AVP. This increased mesangial cell hypertrophy and extracellular matrix synthesis may play a crucial role in the glomerular mesangial expansion common to diabetic nephropathy.
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Ibaraki, Japan. atsuo.tahara@jp.astellas.com
authors.forename: Atsuo
authors.initials: A
authors.lastname: Tahara
authors.forename: Junko
authors.initials: J
authors.lastname: Tsukada
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Tomura
authors.forename: Takeyuki
authors.initials: T
authors.lastname: Yatsu
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shibasaki
mesh_terms: D000818:Animals; D050034:Antidiuretic Agents / Q000494:pharmacology*; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002478:Cells, Cultured; D024141:Collagen Type IV / Q000096:biosynthesis; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000378:metabolism; D006943:Hyperglycemia / Q000503:physiopathology*; D006965:Hyperplasia / Q000188:drug therapy / Q000503:physiopathology; D006984:Hypertrophy / Q000188:drug therapy / Q000503:physiopathology; D050527:Mesangial Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D019311:Staurosporine / Q000494:pharmacology
chemical_list: D050034:Antidiuretic Agents; D024141:Collagen Type IV; D004791:Enzyme Inhibitors; D001127:Arginine Vasopressin; D019311:Staurosporine