Increased hyaluronan production in the glomeruli from diabetic rats: a link between glucose-induced prostaglandin production and reduced sulphated proteoglycan.
Exposure in vivo or in vitro to elevated glucose increases production of vasoactive prostaglandins by glomeruli and mesangial cells. This study aimed to determine whether this increased prostaglandin production could provide a link with later structural changes in diabetic nephropathy. Glomerular cores were prepared from control rats and streptozotocin-diabetic rats (3 weeks' duration). Over 24 h in culture hyaluronan production from diabetic glomerular cores was higher than production from control glomerular cores whether maintained in 5.6 mmol/l glucose (105.6 +/- 15.5 vs 53.6 +/- 8.5 ng hyaluronan per 250 glomerular cores, p < 0.001); in 25 mmol/l glucose (149.3 +/- 34.8 vs 62.7 +/- 7.8 ng hyaluronan per 250 glomerular cores, p < 0.01); or in 45 mmol/l glucose (176.8 +/- 23.3 vs 102.0 +/- 17.9 ng hyaluronan per 250 glomerular cores, p < 0.01). At 5.6 mmol/l glucose, exposure in vitro to prostaglandin E2 caused an increase in hyaluronan production [maximal at 10(-9) mol/l prostaglandin E2, 237 +/- 19 vs 42 +/- 4, ng hyaluronan per 250 glomerular cores, p < 0.001 (control) and 195 +/- 7 vs 103 +/- 5, ng hyaluronan per 250 glomerular cores, p < 0.001 (diabetic)]. In both control and diabetic glomerular cores hyaluronan production was reduced significantly by the cyclooxygenase inhibitor indomethacin (10(-5) mol/l) [24.7 +/- 3.33 vs. 40.25 +/- 4.11 ng hyaluronan per 250 glomerular cores, p < 0.05 (control) and 36.5 +/- 6.25 vs 118.0 +/- 22.6, p < 0.01 (diabetic)]. A direct spectrophotometric microassay was used to determine the concentration of sulphated glycosaminoglycans derived from papain-digested glomerular core proteoglycans.(ABSTRACT TRUNCATED AT 250 WORDS)
Mahadevan
P
P
Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Larkins
R G
RG
Fraser
J R
JR
Fosang
A J
AJ
Dunlop
M E
ME
D000818:Animals; D002478:Cells, Cultured; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000378:metabolism; D006820:Hyaluronic Acid / Q000096:biosynthesis* / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007672:Kidney Cortex / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values
D011508:Chondroitin Sulfate Proteoglycans; D006025:Glycosaminoglycans; D011453:Prostaglandins; D006820:Hyaluronic Acid; D005947:Glucose; D015232:Dinoprostone; D007213:Indomethacin