Glomerular proliferation during early stages of diabetic nephropathy is associated with local increase of sphingosine-1-phosphate levels.
In this study, the effects of short-term diabetes (4 days) on rat renal glomerular cells proliferation and the potential involvement of sphingolipids in this process were investigated. Immunohistochemical analysis showed that streptozotocin (STZ)-induced diabetes promoted increased intra-glomerular hyperplasia, particularly marked for mesangial cells. This was associated with a concomitant increase in neutral ceramidase and sphingosine-kinase activities and the accumulation of the pro-proliferative sphingolipid sphingosine-1-phosphate, in glomeruli isolated from kidney cortex of STZ-treated rats. These results suggest a possible involvement of sphingolipid metabolites in the glomerular proliferative response during the early stages of diabetic nephropathy.
Geoffroy
Karen
K
Diabetic Microangiopathy Research Unit, MERCK Santé, INSERM UMR 585/INSA-Lyon, 69621 Villeurbanne, France.
Troncy
Lysiane
L
Wiernsperger
Nicolas
N
Lagarde
Michel
M
El Bawab
Samer
S
D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation; D055572:Ceramidases; D003928:Diabetic Nephropathies / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology*; D008246:Lysophospholipids / Q000378:metabolism*; D008297:Male; D055576:Neutral Ceramidase; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism*; D013311:Streptozocin / Q000494:pharmacology; D013997:Time Factors; D000099157:Sphingosine Kinase
D000581:Amidohydrolases; D055572:Ceramidases; D008246:Lysophospholipids; D055576:Neutral Ceramidase; D017853:Phosphotransferases (Alcohol Group Acceptor); D013110:Sphingosine; D013311:Streptozocin; D000099157:Sphingosine Kinase; C060506:sphingosine 1-phosphate; C526748:Asah2 protein, rat