• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Jan 1990; 87(1): 404–408.
PMCID: PMC53272

Overexpression of fibronectin induced by diabetes or high glucose: phenomenon with a memory.

Abstract

To identify events and mechanisms that might contribute to the poor reversibility of diabetic complications, we examined whether diabetes or high glucose induces changes in gene expression and whether such changes outlast the presence of the metabolic abnormalities. The study focused on fibronectin because the increased amounts of this glycoprotein found in diabetic tissues and thickened basement membranes are as yet unexplained. In streptozotocin-induced diabetic rats, fibronectin mRNA levels were increased to 304 +/- 295% of control (mean +/- SD) in the kidney cortex (P less than 0.02), and to 271 +/- 273% of control in the heart (P less than 0.02), while actin mRNA levels remained unchanged. Elevation of fibronectin mRNA persisted for weeks after restoration of near-normoglycemia. In cultured human endothelial cells, high glucose-induced overexpression of fibronectin and collagen IV remained detectable after replating and multiple cell divisions in the absence of high glucose. Cells shifted to normal-glucose medium after prolonged exposure to high glucose also exhibited a proliferative advantage over cells chronically maintained in normal glucose. Thus, diabetes increases fibronectin expression in tissues that are known targets of the complications, and the effect is not readily reversible. The in vitro studies suggest that hyperglycemia may be responsible for these events through induction of self-perpetuating changes in gene expression.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.0M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Steffes MW, Sutherland DE, Goetz FC, Rich SS, Mauer SM. Studies of kidney and muscle biopsy specimens from identical twins discordant for type I diabetes mellitus. N Engl J Med. 1985 May 16;312(20):1282–1287. [PubMed]
  • Bohman SO, Tydén G, Wilczek H, Lundgren G, Jaremko G, Gunnarsson R, Ostman J, Groth CG. Prevention of kidney graft diabetic nephropathy by pancreas transplantation in man. Diabetes. 1985 Mar;34(3):306–308. [PubMed]
  • Feingold KR, Lee TH, Chung MY, Siperstein MD. Muscle capillary basement membrane width in patients with vacor-induced diabetes mellitus. J Clin Invest. 1986 Jul;78(1):102–107. [PMC free article] [PubMed]
  • Engerman RL, Kern TS. Progression of incipient diabetic retinopathy during good glycemic control. Diabetes. 1987 Jul;36(7):808–812. [PubMed]
  • Lauritzen T, Frost-Larsen K, Larsen HW, Deckert T. Two-year experience with continuous subcutaneous insulin infusion in relation to retinopathy and neuropathy. Diabetes. 1985 Aug;34 (Suppl 3):74–79. [PubMed]
  • Ramsay RC, Goetz FC, Sutherland DE, Mauer SM, Robison LL, Cantrill HL, Knobloch WH, Najarian JS. Progression of diabetic retinopathy after pancreas transplantation for insulin-dependent diabetes mellitus. N Engl J Med. 1988 Jan 28;318(4):208–214. [PubMed]
  • Steffes MW, Brown DM, Basgen JM, Matas AJ, Mauer SM. Glomerular basement membrane thickness following islet transplantation in the diabetic rat. Lab Invest. 1979 Aug;41(2):116–118. [PubMed]
  • Gøtzsche O, Gundersen HJ, Osterby R. Irreversibility of glomerular basement membrane accumulation despite reversibility of renal hypertrophy with islet transplantation in early experimental diabetes. Diabetes. 1981 Jun;30(6):481–485. [PubMed]
  • Bilous RW, Mauer SM, Sutherland DE, Najarian JS, Goetz FC, Steffes MW. The effects of pancreas transplantation on the glomerular structure of renal allografts in patients with insulin-dependent diabetes. N Engl J Med. 1989 Jul 13;321(2):80–85. [PubMed]
  • Brownlee M, Cerami A, Vlassara H. Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications. N Engl J Med. 1988 May 19;318(20):1315–1321. [PubMed]
  • Hostetter TH, Troy JL, Brenner BM. Glomerular hemodynamics in experimental diabetes mellitus. Kidney Int. 1981 Mar;19(3):410–415. [PubMed]
  • Dillmann WH. Diabetes mellitus induces changes in cardiac myosin of the rat. Diabetes. 1980 Jul;29(7):579–582. [PubMed]
  • Regan TJ, Wu CF, Yeh CK, Oldewurtel HA, Haider B. Myocardial composition and function in diabetes. The effects of chronic insulin use. Circ Res. 1981 Dec;49(6):1268–1277. [PubMed]
  • Weiss MA, Ooi BS, Ooi YM, Engvall E, Ruoslahti E. Immunofluorescent localization of fibronectin in the human kidney. Lab Invest. 1979 Oct;41(4):340–347. [PubMed]
  • Dixon AJ, Burns J, Dunnill MS, McGee JO. Distribution of fibronectin in normal and diseased human kidneys. J Clin Pathol. 1980 Nov;33(11):1021–1028. [PMC free article] [PubMed]
  • Falk RJ, Scheinman JI, Mauer SM, Michael AF. Polyantigenic expansion of basement membrane constituents in diabetic nephropathy. Diabetes. 1983 May;32 (Suppl 2):34–39. [PubMed]
  • Fischer VW, Barner HB, Leskiw ML. Capillary basal laminar thichness in diabetic human myocardium. Diabetes. 1979 Aug;28(8):713–719. [PubMed]
  • Factor SM, Okun EM, Minase T. Capillary microaneurysms in the human diabetic heart. N Engl J Med. 1980 Feb 14;302(7):384–388. [PubMed]
  • Fein FS, Sonnenblick EH. Diabetic cardiomyopathy. Prog Cardiovasc Dis. 1985 Jan-Feb;27(4):255–270. [PubMed]
  • Labat-Robert J, Leutenegger M, Llopis G, Ricard Y, Derouette JC. Plasma and tissue fibronectin in diabetes. Clin Physiol Biochem. 1984;2(1):39–48. [PubMed]
  • Kohno T, Sorgente N, Goodnight R, Ryan SJ. Alterations in the distribution of fibronectin and laminin in the diabetic human eye. Invest Ophthalmol Vis Sci. 1987 Mar;28(3):515–521. [PubMed]
  • Cagliero E, Maiello M, Boeri D, Roy S, Lorenzi M. Increased expression of basement membrane components in human endothelial cells cultured in high glucose. J Clin Invest. 1988 Aug;82(2):735–738. [PMC free article] [PubMed]
  • Baker JR, Metcalf PA, Johnson RN, Newman D, Rietz P. Use of protein-based standards in automated colorimetric determinations of fructosamine in serum. Clin Chem. 1985 Sep;31(9):1550–1554. [PubMed]
  • Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. [PubMed]
  • Jaffe EA, Nachman RL, Becker CG, Minick CR. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest. 1973 Nov;52(11):2745–2756. [PMC free article] [PubMed]
  • Lorenzi M, Cagliero E, Toledo S. Glucose toxicity for human endothelial cells in culture. Delayed replication, disturbed cell cycle, and accelerated death. Diabetes. 1985 Jul;34(7):621–627. [PubMed]
  • Lorenzi M, Nordberg JA, Toledo S. High glucose prolongs cell-cycle traversal of cultured human endothelial cells. Diabetes. 1987 Nov;36(11):1261–1267. [PubMed]
  • Oldberg A, Linney E, Ruoslahti E. Molecular cloning and nucleotide sequence of a cDNA clone coding for the cell attachment domain in human fibronectin. J Biol Chem. 1983 Sep 10;258(17):10193–10196. [PubMed]
  • Weil D, Bernard M, Gargano S, Ramirez F. The pro alpha 2(V) collagen gene is evolutionarily related to the major fibrillar-forming collagens. Nucleic Acids Res. 1987 Jan 12;15(1):181–198. [PMC free article] [PubMed]
  • Yamada KM. Cell surface interactions with extracellular materials. Annu Rev Biochem. 1983;52:761–799. [PubMed]
  • Hynes R. Molecular biology of fibronectin. Annu Rev Cell Biol. 1985;1:67–90. [PubMed]
  • Craven PA, DeRubertis FR. Protein kinase C is activated in glomeruli from streptozotocin diabetic rats. Possible mediation by glucose. J Clin Invest. 1989 May;83(5):1667–1675. [PMC free article] [PubMed]
  • Lee TS, Saltsman KA, Ohashi H, King GL. Activation of protein kinase C by elevation of glucose concentration: proposal for a mechanism in the development of diabetic vascular complications. Proc Natl Acad Sci U S A. 1989 Jul;86(13):5141–5145. [PMC free article] [PubMed]
  • Angel P, Imagawa M, Chiu R, Stein B, Imbra RJ, Rahmsdorf HJ, Jonat C, Herrlich P, Karin M. Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor. Cell. 1987 Jun 19;49(6):729–739. [PubMed]
  • Cagliero E, Barrieux A, Lehman C, Dillmann WH. Diabetes-induced changes of proteins synthesized by adult cardiac myocytes are partially reversed by insulin. J Mol Cell Cardiol. 1988 May;20(5):427–434. [PubMed]
  • Phan-Thanh L, Robert L, Derouette JC, Labat-Robert J. Increased biosynthesis and processing of fibronectin in fibroblasts from diabetic mice. Proc Natl Acad Sci U S A. 1987 Apr;84(7):1911–1915. [PMC free article] [PubMed]
  • Lorenzi M, Goldbaum MH, Spencer EM, Cheney C. Improved diabetic control and retinopathy. N Engl J Med. 1983 Jun 30;308(26):1600–1600. [PubMed]
  • Lauritzen T, Frost-Larsen K, Larsen HW, Deckert T. Effect of 1 year of near-normal blood glucose levels on retinopathy in insulin-dependent diabetics. Lancet. 1983 Jan 29;1(8318):200–204. [PubMed]
  • Zaret KS, Yamamoto KR. Reversible and persistent changes in chromatin structure accompany activation of a glucocorticoid-dependent enhancer element. Cell. 1984 Aug;38(1):29–38. [PubMed]
  • Tam SP, Haché RJ, Deeley RG. Estrogen memory effect in human hepatocytes during repeated cell division without hormone. Science. 1986 Dec 5;234(4781):1234–1237. [PubMed]
  • Raskin P, Pietri AO, Unger R, Shannon WA., Jr The effect of diabetic control on the width of skeletal-muscle capillary basement membrane in patients with Type I diabetes mellitus. N Engl J Med. 1983 Dec 22;309(25):1546–1550. [PubMed]
  • Cohen MP, Khalifa A. Renal glomerular collagen synthesis in streptozotocin diabetes. Reversal of increased basement membrane synthesis with insulin therapy. Biochim Biophys Acta. 1977 Dec 22;500(2):395–404. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...