title: Angiotensin-converting enzyme inhibition modulates high-glucose-induced extracellular matrix changes in mouse glomerular epithelial cells.
abstract: OBJECTIVE
  Extracellular matrix alterations are involved in the pathogenesis of diabetic nephropathy. We evaluated the effects of high glucose concentrations and inhibition of angiotensin-converting enzyme on the laminin and fibronectin production by glomerular epithelial cells.
  
  
  METHODS
  Glomerular epithelial cells were cultured in 5 and 30 mmol/l glucose, with and without enalaprilat (0.3 mmol/l). Laminin and fibronectin were measured (35S-methionine, immunoprecipitation), and their mRNA expression was evaluated (RT-PCR).
  
  
  RESULTS
  The laminin concentration was higher in the cells than in the medium, where an increase of its content was observed under high-glucose conditions (p < 0.01). Fibronectin, found only in the medium, was not modified by the high glucose concentration. Following enalaprilat administration, the laminin concentration was decreased under high-glucose conditions, both in the cell and in the medium (p < 0.001), whereas the fibronectin concentration was increased under high-glucose conditions (p < 0.001). The mRNA expression of laminin and fibronectin under high-glucose conditions only slightly increased. Enalaprilat decreased the fibronectin mRNA synthesis dramatically (>50%, p < 0.0001) under high-glucose conditions.
  
  
  CONCLUSIONS
  Enalaprilat normalizes the abnormal, high-glucose-induced concentration of laminin, while it decreases the fibronectin synthesis. The improvement of the renal function in diabetic patients treated with angiotensin-converting enzyme inhibitors may, in part, be due to a modulator effect on extracellular matrix content and composition.
authors.affiliation: Division of Endocrinology, Department of Clinical Sciences, Clinica Medica 2, Rome, Italy. susanna.morano@uniroma1.it
authors.forename: S
authors.initials: S
authors.lastname: Morano
authors.forename: R
authors.initials: R
authors.lastname: Cipriani
authors.forename: M G
authors.initials: MG
authors.lastname: Cerrito
authors.forename: C
authors.initials: C
authors.lastname: Santangelo
authors.forename: F
authors.initials: F
authors.lastname: Vasaturo
authors.forename: F
authors.initials: F
authors.lastname: Pantellini
authors.forename: M
authors.initials: M
authors.lastname: Sensi
authors.forename: L
authors.initials: L
authors.lastname: Guidobaldi
authors.forename: S
authors.initials: S
authors.lastname: Scarpa
authors.forename: U
authors.initials: U
authors.lastname: Di Mario
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D015773:Enalaprilat / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D007678:Kidney Glomerulus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007797:Laminin / Q000235:genetics / Q000378:metabolism; D051379:Mice; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D005353:Fibronectins; D007797:Laminin; D012333:RNA, Messenger; D007703:Peptidyl-Dipeptidase A; D015773:Enalaprilat; D005947:Glucose