Journal Mobile Options
Table of Contents
Vol. 88, No. 4, 2001
Issue release date: 2001

Hyaluronan and Rat Renal Fibroblasts: In vitro Studies

Pedagogos E. · Hewitson T.D. · Nicholls K.M. · Becker G.J.
To view the fulltext, log in and/or choose pay-per-view option

Individual Users: Register with Karger Login Information

Please create your User ID & Password





Contact Information











I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in

Abstract

Hyaluronic acid (HA) is a ubiquitous component of extracellular matrix. After tissue injury, HA appears in greater abundance during the inflammatory response and the phase of clearance of cell and matrix debris, before collagen production and matrix degradation. The aim of this study was to examine whether normal rat renal fibroblasts were capable of HA synthesis and to determine the effect of HA on in vitro collagen production in a series of normal rat cortical fibroblast cultures. Fibroblast cultures from both renal cortex and medulla were established from adult Sprague-Dawley rats. HA synthesis was measured by radioimmunoassay, and incorporation of 3H-proline into collagen was used to determine collagen synthesis. Fibroblasts were defined on the basis of morphology and alpha smooth muscle actin immunohistochemistry. HA synthesis was measured in both renal cortical and medullary fibroblasts at passage 3 for both 24 and 48 h in 5 animals and expressed as a fraction of protein content. HA was synthesized by both cortical and medullary fibroblasts; however, cortical fibroblasts produced less HA than medullary fibroblasts at both 24 h (p = 0.05) and 48 h (p = 0.02). In normal cortical fibroblasts, exogenous HA suppressed overall total (cell and media) collagen production after a 22-hour labelling period (p = 0.002 compared to controls). Decreased collagen production was also found individually in cell (p = 0.02) and media fractions (p = 0.01). Both cortical and medullary fibroblasts are capable of synthesizing HA in vitro. Furthermore, the findings in this study suggest that HA may be an important mediator in reducing renal cortical fibroblast collagen production and may play an important role in limiting renal interstitial scarring.



Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Alexander SA, Donoff B: The glycosaminoglycans of open wounds. J Surg Res 1980;29:422–429.

    External Resources

  2. Toole BP: Hyaluronate-cell interactions and growth factor regulation of hyaluronate synthesis during limb development; in Evered D, Whelan J (eds): The Biology of Hyaluronan. Chichester Wiley & Sons, 1989, pp 138–145.
  3. Copp AJ, Bernfield M: Glycosaminoglycans vary in accumulation along the neuraxis during spinal neurulation in the mouse embryo. Dev Biol 1988;130:573–582.
  4. Farber SJ, van Prang D: Composition of glycosaminoglycans (mucopolysaccharides) in rabbit renal papillae. Biochim Biophys Acta 1970;208:219–226.

    External Resources

  5. Vasan NS, Saporito SA, Saraswathi S, Tesoriero JV, Manley S: Alterations of renal cortex and medullary glycosaminoglycans in ageing dog kidney. Biochim Biophys Acta 1983;760:197–205.

    External Resources

  6. Sibalic V, Fan X, Loffing J, Wuthrich RP: Upregulated renal tubular CD44, hyaluronan, and osteopontin in kdkd mice with interstitial nephritis. Nephrol Dial Transplant 1997;7:1344–1353.
  7. Wu JC, Fan GM, Kitazawa K, Sugisaki T: The relationship of adhesion molecules and leukocytes infiltration in chronic tubulointerstitial nephritis induced by puromycin aminonucleoside in Wistar rats. Clin Immunol Immunopathol 1996;79:229–235.
  8. Nishikawa K, Andres G, Bhan AK, McCluskey RT, Collins AB, Stow JL, Stamenkovic I: Hyaluronate is a component of crescents in rat autoimmune glomerulonephritis. Lab Invest 1993;68:146–153.
  9. Wells A, Larsson E, Tengblad A, Fellstrom TG, Klareskog L, Laurent TC: The localisation of hyaluronan in normal and rejected human kidneys. Transplantation 1990;50:240–243.
  10. Hammerman D, Wood DD: Interleukin-1 enhances synovial cell hyaluronate synthesis. Proc Soc Exp Biol Med 1984;177:205–210.

    External Resources

  11. Heldin P, Laurent TC, Heldin GH: Effect of growth factors on hyaluronan synthesis in cultured human fibroblasts. Biochem J 1989;258:919–922.
  12. Postlethwaite AE, Smith GN, Lachman LB, Endres RO, Poppleton HM, Hasty KA, Seyer JM, Kang AH: Stimulation of glycosaminoglycan synthesis in cultured human dermal fibroblasts by interleukin-1. J Clin Invest 1989;83:629–636.

    External Resources

  13. Wiggins R, Goyal M, Merritt S, Killen PD: Vascular adventitial cell expression of collagen I messenger ribonucleic acid in anti-glomerular basement membrane antibody induced crescentic nephritis in the rabbit: A cellular source for interstitial collagen synthesis in inflammatory renal disease. Lab Invest 1993;68:557–565.
  14. Johnson RJ, Alpers CE, Yoshimura A, Lombardi D, Pritzl P, Floege J, Schwartz SM: Renal injury from angiotensin-II-mediated hypertension. Hypertension 1992;19:464–474.
  15. Zhang G, El Nahas AM: Alpha-smooth muscle actin positive cell: Predictors of experimental renal fibrosis. J Am Soc Nephrol 1994;5:824.
  16. Hewitson TD, Becker GJ: Myofibroblast involvement in renal interstitial fibrosis. Nephrology 1996;2:229–234.
  17. Fine A, Poliks CF, Donahue LP, Smith BD, Goldstein RH: The differential effect of prostaglandin E2 on transforming growth factor-β and insulin-induced collagen formation in lung fibroblasts. J Biol Chem 1989;264:16988–16991.
  18. Varga J, Diaz-Perez A, Rosenbloom J, Jimenez SA: PGE2 causes a coordinate decrease in steady-state levels of fibronectin and types I and III procollagen mRNAs in normal human dermal fibroblasts. Biochem Biophys Res Commun 1987;147:1282–1288.
  19. Mast BA, Haynes JH, Krummel TM, Diegelmann RF, Cohen IK: In vivo degradation of fetal wound hyaluronic acid results in increased fibroplasia, collagen deposition, and neovascularization. Plast Reconstr Surg 1992;89:503–509.
  20. Ellis I, Grey AM, Schor AM, Schor SL: Antagonistic effects of TGF-beta 1 and MSF on fibroblast migration and hyaluronic acid synthesis: Possible implications for dermal wound healing. J Cell Sci 1992;102:447–456.

    External Resources

  21. Mast BA, Flood LC, Haynes JH, DePalma RL, Cohen IK, Diegelmann RF, Krummel TM: Hyaluronic acid is a major component of the matrix of fetal rabbit skin and wounds. Implications for healing by regeneration. Matrix 1991;11:63–68.
  22. Shepard S, Becker H, Hartmann JX: Using hyaluronic acid to create a fetal-like environment in vitro. Ann Plast Surg 1996;36:65–69.
  23. Laurent TC, Fraser JRE: Hyaluronan. FASEB J 1992;6:2397–2404.
  24. DePalma RL, Krummel TM, Durham LA, Michna BA, Thomas BL, Nelson JM, Diegelmann RF: Characterization and quantitation of wound matrix in the fetal rabbit. Matrix 1989;9:224–231.

    External Resources

  25. Burrington JD: Wound healing in the fetal lamb. J Pediatr Surg 1971;6:523–528.

    External Resources

  26. Rydell N: Decreased granulation tissue reaction after installment of hyaluronic acid. Acta Orthop Scand 1970;41:307–311.

    External Resources

  27. Fullerton MJ, Funder JW: Aldosterone and cardiac fibrosis: In vitro studies. Cardiovasc Res 1994;28:1863–1867.
  28. Hallgren R, Gerdin B, Tufveson G: Hyaluronic acid accumulation and redistribution in rejecting rat kidney graft: Relationship to the transplantation edema. J Exp Med 1990;171:2063–2076.

    External Resources

  29. Frost SJ, Weigel PH: Binding of hyaluronic acid to mammalian fibrinogens. Biochim Biophys Acta 1990;1034:39–45.
  30. Bjermer A, Engstrom-Laurent A, Lundgren R, Rosenhall L, Hallgren R: Hyaluronic acid and procollagen III peptide in bronchoalveolar lavage fluid as indicators of lung disease activity in farmer’s lung. Br Med J 1987;295:801–806.
  31. Sopher D: A study of wound healing in the fetal tissues of the cynomolgus monkey. Lab Anim Handb 1975;6:327–335.
  32. Goss AN: Intra-uterine healing of fetal rat oral mucosal, skin and cartilage wounds. J Oral Pathol 1977;6:35–43.

    External Resources

  33. Borchelt BD, Krummel TM, Cawthorn JW, Thomas BL, Diegelmann RF, Cohen IK: Transposition of an early adult wound to a fetal rabbit wound does not result in recruitement of fibroblasts. Surg Forum 1989;40:555–557.
  34. Ellis I, Schor SL: The interdependent modulation of hyaluronan synthesis by TGF-β1 and extracellular matrix: Consequences for the control of cell migration. Growth Factors 1995;12:211–222.
  35. Chiu ES, Longaker MT, Adzick NS, Stern M, Harrison MR, Stern R: Hyaluronic acid patterns in fetal and adult wound fluid. Surg Forum 1990;41:636–639.
  36. Toole BP: Developmental role of hyaluronate. Connect Tissue Res 1982;10:93–100.

    External Resources

  37. St. Onge R, Weiss C, Denlinger JL, Balazs EA: A preliminary assessment of Na-hyaluronate injection into ‘no man’s land’ for primary flexor tendon repair. Clin Orthop 1980;146:269–275.

    External Resources

  38. Laurent C, Helsstrom S, Stenfors L: Hyaluronic acid reduces connective tissue formation in middle ears filled with absorbable gelatin sponge: An experimental study. Am J Otolaryngol 1986;7:181–186.

    External Resources



Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50