Angiotensin-converting enzyme inhibition modulates high-glucose-induced extracellular matrix changes in mouse glomerular epithelial cells.
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.
Morano
S
S
Division of Endocrinology, Department of Clinical Sciences, Clinica Medica 2, Rome, Italy. susanna.morano@uniroma1.it
Cipriani
R
R
Cerrito
M G
MG
Santangelo
C
C
Vasaturo
F
F
Pantellini
F
F
Sensi
M
M
Guidobaldi
L
L
Scarpa
S
S
Di Mario
U
U
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
D000806:Angiotensin-Converting Enzyme Inhibitors; D005353:Fibronectins; D007797:Laminin; D012333:RNA, Messenger; D007703:Peptidyl-Dipeptidase A; D015773:Enalaprilat; D005947:Glucose