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Increased hyaluronan production in the glomeruli from diabetic rats: a link between glucose-induced prostaglandin production and reduced sulphated proteoglycan
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  • Originals
  • Published: March 1995

Increased hyaluronan production in the glomeruli from diabetic rats: a link between glucose-induced prostaglandin production and reduced sulphated proteoglycan

  • P. Mahadevan1,
  • R. G. Larkins1,
  • J. R. E. Fraser1,
  • A. J. Fosang1 &
  • …
  • M. E. Dunlop1 

Diabetologia volume 38, pages 298–305 (1995)Cite this article

  • 254 Accesses

  • 52 Citations

  • Metrics details

Summary

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. Release of sulphated glycosaminoglycans from diabetic glomerular cores maintained at 5.6 mmol/l glucose was decreased [41.9±1.1 vs 54.0±1.0 Μg of sulphated glycosaminoglycans (chondroitin sulphate) per 250 glomerular cores p<0.01]. A decrease in sulphated glycosaminoglycans was also shown from control glomerular cores maintained at 25 mmol/l glucose. At this glucose concentration, addition of exogenous hyaluronan or prostaglandin E2 significantly reduced sulphated glycosaminoglycans from control and diabetic glomerular cores. It is concluded that increased prostaglandin production secondary to high glucose environment can lead to an increased glomerular hyaluronan synthesis. This can substantially affect the levels of sulphated glycosaminoglycans in the extracellular matrix. We propose that these effects provide a possible link between the initial biochemical consequences of hyperglycaemia and later structural changes seen in the glomerulus in diabetes.

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Abbreviations

PG:

Prostaglandins

GC:

glomerular cores

STZ-D:

streptozotocin diabetes

GAG:

sulphated glycosaminoglycans

PDGF:

platelet derived growth factor

PGE2 :

prostaglandin E2

STZ:

streptozotocin

HSPG:

heparan sulphate proteoglycan

HA:

hyaluronan

References

  1. Kreisberg JI, Patel PY (1983) The effects of insulin, glucose and diabetes on prostaglandin production by rat kidney glomeruli and cultured glomerular mesangial cells. Prostaglandins Leukotrienes Med 11: 431–432

    Article  Google Scholar 

  2. Schambelan M, Blake S, Sraer J, Bens M, Nivez M-P, Wahbe F (1985) Increased prostaglandin production by glomeruli isolated from rats with streptozotocin-induced diabetes mellitus. J Clin Invest 75: 404–412

    PubMed  Google Scholar 

  3. Craven PA, Caines MA, DeRubertis FR (1987) Sequential alterations in glomerular prostaglandin and thromboxane synthesis in diabetic rats: relationship to the hyperfiltration of early diabetes. Metabolism 36: 95–103

    Article  PubMed  Google Scholar 

  4. Esmatjes E, Fernandez MR, Halperin I et al. (1985) Renal hemodynamic abnormalities in patients with short term insulin-dependent diabetes mellitus: role of renal PGs. J Clin Endocrinol Metab 60: 1231–1237

    PubMed  Google Scholar 

  5. Dunlop M, Keogh R, Larkins RG (1993) Fibronectin-induced increase in mesangial cell prostaglandin release: effect of hyperglycemia and PKC inhibition. Diabetes 42: 183–190

    PubMed  Google Scholar 

  6. Craven PA, De Rubertis FR (1989) PKC is activated in glomeruli from streptozotocin diabetic rats: possible mediation by glucose. J Clin Invest 83: 1667–1675

    PubMed  Google Scholar 

  7. Craven PA, Davidson CM, De Rubertis FR (1990) Increase in diacylglycerol mass in isolated glomeruli by glucose from de novo synthesis of glycerolipids. Diabetes 39: 667–674

    PubMed  Google Scholar 

  8. Dunlop ME, Larkins RG (1990) Persistence in culture of increased de novo synthesis of diacylglycerol, phospholipase A2 activity and prostaglandin production by mesangial cells of diabetic rats. Diabetes [Suppl 1] 39:189A (Abstract)

    Google Scholar 

  9. Ayo SH, Radnik R, Garoni JA, Troyer DA, Kreisberg JI (1991) High glucose increases diacylglycerol mass and activates PKC in mesangial cell cultures. Am J Physiol 261: F571-F577

    PubMed  Google Scholar 

  10. Craven PA, Patterson MC, De Rubertis FR (1988) Role of enhanced arachidonate availability through phospholipase A2 pathway in mediation of increased prostaglandin synthesis by glomeruli from diabetic rats. Diabetes 37: 429–435

    PubMed  Google Scholar 

  11. Williams B, Schrier RW (1993) Glucose-induced protein kinase C activity regulates arachidonic acid release and prostaglandin production by cultured rat glomerular mesangial cells. J Clin Invest 92: 2889–2896

    PubMed  Google Scholar 

  12. DeRubertis FR, Craven PA (1994) Activation of protein kinase C in glomerular cells in diabetes. Mechanisms and potential links to the pathogenesis of diabetic glomerulopathy. Diabetes 43: 1–8

    PubMed  Google Scholar 

  13. Kasiske BL, O'Donnell MP, Keane WF (1985) Glucose-induced increases in renal hemodynamic function: possible modulation by renal prostaglandins. Diabetes 34: 360–364

    PubMed  Google Scholar 

  14. Cohen MP, Surma ML (1981) [35S]-sulfate incorporation into glomerular basement membrane glycosaminoglycan is decreased in experimental diabetes. J Lab Clin Med 98: 715–721

    PubMed  Google Scholar 

  15. Brown DM, Klein DJ, Michael AF, Oegema Jr TR (1985) 35S-glycosaminoglycan and 35S-glycopeptide metabolism by diabetic glomeruli and aorta. Diabetes 31: 418–425

    Google Scholar 

  16. Parthasarathy N, Spiro RG (1982) Effect of diabetes on the glycosaminoglycan component of the human glomerular basement membrane. Diabetes 31: 738–741

    PubMed  Google Scholar 

  17. Cohen MP, Klepser H, Wu V-Y (1988) Undersulphation of glomerular basement membrane heparan sulphate in experimental diabetes and lack of correction with aldose reductase inhibitors. Diabetes 37: 1324–1327

    PubMed  Google Scholar 

  18. Kanwar YS, Farquhar MG (1979) Presence of heparan sulfate in the glomerular basement membrane. Proc Natl Acad Sci USA 76: 1303–1307

    PubMed  Google Scholar 

  19. Olgemöller B, Shwaabe S, Gerbitz KD, Scleicher ED (1992) Elevated glucose decreases the content of a basement membrane associated heparan sulphate proteoglycan in proliferating cultured porcine mesangial cells. Diabetologia 35: 183–186

    PubMed  Google Scholar 

  20. Tomida M, Koyama H, Ono T (1977) Effects of adenosine 3′∶5′-cyclic monophosphate and serum on synthesis of hyaluronic acid in confluent rat fibroblasts. Biochem J 162: 539–543

    PubMed  Google Scholar 

  21. Castor W (1974) Connective tissue activation. VII. Evidence supporting a role for prostaglandins and cyclic nucleotides. Connective Tissue Activation 85: 392–402

    Google Scholar 

  22. Yaron M, Yaron I, Wiletzki C, Zor U (1978) Interrelationship between stimulation of prostaglandin E and hyaluronate production by poly (I), poly (C) and interferon in synovial fibroblast culture. Arthritis Rheum 21: 694–698

    PubMed  Google Scholar 

  23. Honda A, Sekiguchi Y, Mori Y (1993) Prostaglandin E2 stimulates cyclic AMP-mediated hyaluronan synthesis in rabbit pericardial mesothelial cells. Biochem J 292: 497–502

    PubMed  Google Scholar 

  24. Laurent TC (1989) Introduction In: Evered D, Whelan J (eds) The biology of hyaluronan. Wiley Chichester (Ciba Foundation Symposium) 143: 1–5

  25. Peach RJ, Hollenbaugh D, Stamenkovic I, Aruffo A (1993) Identification of hyaluronic acid binding site in the extra-cellular domain of CD44. J Cell Biol 122: 257–264

    Article  PubMed  Google Scholar 

  26. McGuire PG, Catellot J, Orkin RW (1987) Size-dependent hyaluronate degradation by cultured cells. J Cell Physiol 133: 267–276

    PubMed  Google Scholar 

  27. Heldin P, Laurent TC, Heldin GH (1989) Effect of growth factors on hyaluronan synthesis in cultured human fibroblasts. Biochem J 258: 919–922

    PubMed  Google Scholar 

  28. Honda A, Iwai T, Mori Y (1989) Insulin-like growth factor I (IGF-I) enhances hyaluronic acid synthesis in rabbit pericardium. Biochem Biophys Acta 1014: 305–312

    Article  PubMed  Google Scholar 

  29. Weibkin OW, Muir H (1977) Synthesis of proteoglycans by suspension and monolayer cultures of adult chondrocytes and de novo cartilage nodules — the effect of hyaluronic acid. J Cell Sci 27: 199–211

    PubMed  Google Scholar 

  30. Mason RM, Crossman MV, Sweeney C (1989) Hyaluronan and hyaluronanbinding proteins in cartilagenous tissues. The biology of hyaluronan. Wiley Chichester (Ciba Foundation Symposium) 143: 107–120

    Google Scholar 

  31. Handley CJ, Lowther DA (1986) Inhibition of proteoglycan biosynthesis by hyaluronic acid in chondrocytes in cell culture. Biochim Biophys Acta 444: 69–74

    Google Scholar 

  32. Shimazu A, Jikko A, Iwamoto M et al. (1993) Effects of hyaluronic acid on the release of proteoglycan from the cell matrix in rabbit chondrocyte cultures in the presence and absence of cytokines. Arthritis Rheum 36: 247–253

    PubMed  Google Scholar 

  33. Brandt R, Hedolf E, Asman I, Bucht A, Tengblad A (1987) A convenient radiometric assay for hyaluronan. Acta Otolar 442: 31–35

    Google Scholar 

  34. Dunlop ME, Larkins RG (1990) Insulin-dependent contractility of glomerular mesangial cells in response to angiotensin II, platelet activating factor and endothelin is attenuated by prostaglandin E2. Biochem J 272: 561–568

    PubMed  Google Scholar 

  35. Hassis A, Pidikiti N, Gamero D (1986) Effects of vasoactive peptides on cytosolic calcium in cultured mesangial cells. Am J Physiol 251: F1018-F1028

    PubMed  Google Scholar 

  36. Ratcliffe A, Doherty M, Mairi RN, Hardingham TE (1988) Increased levels of proteoglycan components in the synovial fluids of patients with acute joint disease. Ann Rheum Dis 47: 826–832

    PubMed  Google Scholar 

  37. Farndale RW, Sayers CA, Barrett AJ (1982) A direct spectrophotometric microassay for sulfated glycosaminoglycans in cartilage cultures. Conn Tiss Res 9: 247–248

    Google Scholar 

  38. Sochor M, Zaheer Baquer N, McLean P (1979) Regulation of pathways of glucose metabolism in the kidney. The effect of experimental diabetes on the activity of the pentose phosphate pathway and the glucuronate-xylulose pathway. Arch Biochem Biophys 198: 632–646

    PubMed  Google Scholar 

  39. Butler DM, Vitti GF, Leizer T, Hamilton JA (1988) Stimulation of the hyaluronic acid levels of human synovial fibroblasts by recombinant human tumor necrosis factor α, tumor necrosis factor Β, interleukin 1α and interleukin 1Β. Arthritis Rheum 31: 1281–1289

    PubMed  Google Scholar 

  40. Hata R, Sunada H, Arai K, Sato T, Ninomiya Y, Nagai Y, Senoo H (1988) Regulation of collagen metabolism and cell growth in cultured skin fibroblasts. Eur J Biochem 173: 261–267

    PubMed  Google Scholar 

  41. Uzuka M, Nakajima K, Ohta S, Mori Y (1980) The mechanism of estrogen-induced increase in hyaluronic acid biosynthesis, with special reference to estrogen receptor in the mouse skin. Biochim Biophys Acta 627: 199–206

    PubMed  Google Scholar 

  42. Postlethwaite AE, Smith GN, Lachman LB et al. (1989) Stimulation of glycosaminoglycan synthesis in cultured human dermal fibroblasts by interleukin 1. J Clin Invest 83: 629–636

    PubMed  Google Scholar 

  43. Prehm P (1980) Induction of hyaluronic acid synthesis in teratocarcinoma stem cells by retinoic acid. FEBS Lett 111: 295–298

    Article  PubMed  Google Scholar 

  44. Heldin P, Asplund T, Ytterberg D, Thelin S, Laurent T (1992) Characterization of the molecular mechanism involved in the activation of hyaluronan synthetase by platelet derived growth factor in human mesothelial cells. Biochem J 283: 165–170

    PubMed  Google Scholar 

  45. Lansing M, Lellig S, Mausolf et al. (1993) Hyaluronate synthase: cloning and sequencing of the gene from Streptococcus sp. Biochem J 289: 179–184

    PubMed  Google Scholar 

  46. Heickendorff L, Ledet T, Rasmussen LM (1994) Glycosaminoglycans in the human aorta in diabetes mellitus: a study of the tunica media from areas with and without atherosclerotic plaque. Diabetologia 37: 286–292

    Article  PubMed  Google Scholar 

  47. Templeton DM (1989) Retention of glomerular basement membrane-proteoglycans accompanying loss of anionic site staining in experimental diabetes. Lab Invest 61: 202–211

    PubMed  Google Scholar 

  48. Rohrbach R (1986) Reduced content and abnormal distribution of anionic sites (acid proteoglycans) in the diabetic glomerular basement membrane. Virchows Arch B Cell Path 51: 127–135

    Google Scholar 

  49. Mason RM, Thomas G, Davies M (1992) Proteoglycan synthesis by human mesangial cells is depressed by hyperglycemic glucose concentrations. Biochem Soc Transactions 20: 20 (Abstract)

    Google Scholar 

  50. Hardingham TE, Fosang AJ (1992) Proteoglycans: many forms and many functions. Faseb J 6: 861–870

    PubMed  Google Scholar 

  51. LeBaron RG, Hook A, Esko JD, Gay JS, Hook M (1989) Binding of heparan sulfate to type V collagen. J Biol Chem 264: 7950–7956

    PubMed  Google Scholar 

  52. Stamatoglou SC, Keller JM (1982) Interactions of cellular glycosaminoglycans with plasma fibronectin and collagen. Biochim Biophys Acta 719: 90–97

    PubMed  Google Scholar 

  53. Schmidt G, Robenek H, Harrach B et al. (1987) Interaction of small dermatan sulfate proteoglycan from fibroblasts with fibronectin. J Cell Biol 104: 1683–1691

    Article  PubMed  Google Scholar 

  54. Pringle GA, Dodd CM (1990) Immunoelectron microscopic localizations of the core protein of decorin near the d and e bands of tendon collagen fibrils by use of monoclonal antibodies. J Histochem Cytochem 38: 1405–1411

    PubMed  Google Scholar 

  55. Vogel KG, Paulsson M, Heingard D (1984) Specific inhibition of type I and type II collagen fibrillogenesis by the small proteoglycan of tendon. Biochem J 223: 587–597

    PubMed  Google Scholar 

  56. Oldberg A, Ruoslahti E (1982) Interactions between chondroitin sulfate proteoglycan, fibronectin, and collagen. J Biol Chem 257: 4859–4863

    PubMed  Google Scholar 

  57. Silbiger S, Schlondorff D, Crowley S et al. (1993) The effect of glucose on proteoglycans produced by cultured mesangial cells. Diabetes 42: 1815–1822

    PubMed  Google Scholar 

  58. Sirek OV, Sirek A, Cukerman E (1980) Arterial glycosaminoglycans in diabetic dogs. Blood Vessels 17: 271–275

    PubMed  Google Scholar 

  59. Axellesson I, Lorentzon R, Pita JC (1983) Biosynthesis of rat growth plate proteoglycans in diabetes and malnutrition. Calcif Tissue Int 35: 237–242

    PubMed  Google Scholar 

  60. Kjellen L, Bielefeld D, Hook M (1983) Reduced sulfation of liver heparan sulfate in experimentally diabetic rats. Diabetes 32: 337–342

    PubMed  Google Scholar 

  61. Sraer J, Sraer JD, Chansel D, Russo-Marie F, Kouznetzova B, Ardaillou R (1979) Prostaglandin synthesis by isolated rat renal glomeruli. Mol Cell Endocrinol 16: 29–37

    Article  PubMed  Google Scholar 

  62. Schlondorff D, Roczniak S, Satriano JA, Folkert VW (1980) Prostaglandin synthesis by isolated rat glomeruli, effect of angiotensin II. Am J Physiol 239 (Renal Fluid Electrolyte Physiol 8): F486-F459

    PubMed  Google Scholar 

  63. Schlondorff D, Aynedjian HS, Satriano JA, Bank N (1987) In vivo demonstration of glomerular PGE2 responses to physiological manipulations and experimental agents. Am J Physiol 252 (Renal Fluid Electrolyte Physiol 21): F717-F723

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Royal Melbourne Hospital, University of Melbourne, 3050, Parkville, Victoria, Australia

    P. Mahadevan, R. G. Larkins, J. R. E. Fraser, A. J. Fosang &  M. E. Dunlop

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  1. P. Mahadevan
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  2. R. G. Larkins
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  3. J. R. E. Fraser
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  4. A. J. Fosang
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  5. M. E. Dunlop
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Mahadevan, P., Larkins, R.G., Fraser, J.R.E. et al. Increased hyaluronan production in the glomeruli from diabetic rats: a link between glucose-induced prostaglandin production and reduced sulphated proteoglycan. Diabetologia 38, 298–305 (1995). https://doi.org/10.1007/BF00400634

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  • Received: 19 July 1994

  • Revised: 05 October 1994

  • Issue Date: March 1995

  • DOI: https://doi.org/10.1007/BF00400634

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Key words

  • Hyaluronan
  • prostaglandin
  • sulphated proteoglycan
  • glycosaminoglycan
  • mesangial cell
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