Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1995 Jun;95(6):2862–2867. doi: 10.1172/JCI117992

Regulation of rat mesangial cell growth by diadenosine phosphates.

S Heidenreich 1, M Tepel 1, H Schlüter 1, B Harrach 1, W Zidek 1
PMCID: PMC295973  PMID: 7769127

Abstract

The newly recognized human endogenous vasoconstrictive dinucleotides, diadenosine pentaphosphate (AP5A) and diadenosine hexaphosphate (AP6A), were tested for growth stimulatory effects in rat mesangial cells (MC). Both AP5A and AP6A stimulated growth in micromolar concentrations. The growth stimulatory effect exceeded that of ATP, alpha,beta-methylene ATP, adenosine 5'-O-(3-thio)triphosphate and UTP. Both diadenosine phosphates potentiated the growth response to platelet-derived growth factor, but not to insulin-like growth factor-1. To further elucidate the site of action in the cell cycle, RNA and protein synthesis were assessed. AP5 and AP6A stimulated protein synthesis, but not RNA formation. Furthermore, both agents increased cytosolic free Ca2+ concentration. It is concluded that AP5A and AP6A may play a regulatory role in MC growth as progression factors and possibly modify MC proliferation in glomerular disease.

Full text

PDF
2865

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Agha A., Schlüter H., König S., Biel K., Tepel M., Zidek W. A novel platelet-derived renal vasoconstrictor agent in normotensives and essential hypertensives. J Vasc Res. 1992 May-Jun;29(3):281–289. doi: 10.1159/000158943. [DOI] [PubMed] [Google Scholar]
  2. Baril E. F., Coughlin S. A., Zamecnik P. C. 5',5'''-P1, P4 diadenosine tetraphosphate (Ap4A): a putative initiator of DNA replication. Cancer Invest. 1985;3(5):465–471. doi: 10.3109/07357908509039808. [DOI] [PubMed] [Google Scholar]
  3. Bonventre J. V., Weber P. C., Gronich J. H. PAF and PDGF increase cytosolic [Ca2+] and phospholipase activity in mesangial cells. Am J Physiol. 1988 Jan;254(1 Pt 2):F87–F94. doi: 10.1152/ajprenal.1988.254.1.F87. [DOI] [PubMed] [Google Scholar]
  4. Busse R., Ogilvie A., Pohl U. Vasomotor activity of diadenosine triphosphate and diadenosine tetraphosphate in isolated arteries. Am J Physiol. 1988 May;254(5 Pt 2):H828–H832. doi: 10.1152/ajpheart.1988.254.5.H828. [DOI] [PubMed] [Google Scholar]
  5. Doi T., Striker L. J., Elliot S. J., Conti F. G., Striker G. E. Insulinlike growth factor-1 is a progression factor for human mesangial cells. Am J Pathol. 1989 Feb;134(2):395–404. [PMC free article] [PubMed] [Google Scholar]
  6. Erlinge D., Yoo H., Edvinsson L., Reis D. J., Wahlestedt C. Mitogenic effects of ATP on vascular smooth muscle cells vs. other growth factors and sympathetic cotransmitters. Am J Physiol. 1993 Oct;265(4 Pt 2):H1089–H1097. doi: 10.1152/ajpheart.1993.265.4.H1089. [DOI] [PubMed] [Google Scholar]
  7. Floege J., Eng E., Young B. A., Alpers C. E., Barrett T. B., Bowen-Pope D. F., Johnson R. J. Infusion of platelet-derived growth factor or basic fibroblast growth factor induces selective glomerular mesangial cell proliferation and matrix accumulation in rats. J Clin Invest. 1993 Dec;92(6):2952–2962. doi: 10.1172/JCI116918. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Floege J., Eng E., Young B. A., Johnson R. J. Factors involved in the regulation of mesangial cell proliferation in vitro and in vivo. Kidney Int Suppl. 1993 Jan;39:S47–S54. [PubMed] [Google Scholar]
  9. Ganz M. B., Pekar S. K., Perfetto M. C., Sterzel R. B. Arginine vasopressin promotes growth of rat glomerular mesangial cells in culture. Am J Physiol. 1988 Nov;255(5 Pt 2):F898–F906. doi: 10.1152/ajprenal.1988.255.5.F898. [DOI] [PubMed] [Google Scholar]
  10. Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
  11. Haneda M., Kikkawa R., Koya D., Uzu T., Maeda S., Togawa M., Shigeta Y. Alteration of mesangial response to ANP and angiotensin II by glucose. Kidney Int. 1993 Sep;44(3):518–526. doi: 10.1038/ki.1993.276. [DOI] [PubMed] [Google Scholar]
  12. Harper P. A., Robinson J. M., Hoover R. L., Wright T. C., Karnovsky M. J. Improved methods for culturing rat glomerular cells. Kidney Int. 1984 Dec;26(6):875–880. doi: 10.1038/ki.1984.231. [DOI] [PubMed] [Google Scholar]
  13. Hazelton B., Mitchell B., Tupper J. Calcium, magnesium, and growth control in the WI-38 human fibroblast cell. J Cell Biol. 1979 Nov;83(2 Pt 1):487–498. doi: 10.1083/jcb.83.2.487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Heidenreich S., Gong J. H., Schmidt A., Nain M., Gemsa D. Macrophage activation by granulocyte/macrophage colony-stimulating factor. Priming for enhanced release of tumor necrosis factor-alpha and prostaglandin E2. J Immunol. 1989 Aug 15;143(4):1198–1205. [PubMed] [Google Scholar]
  15. Heidenreich S., Tepel M., Lang D., Rahn K. H., Zidek W. Differential effects of insulin-like growth factor I and platelet-derived growth factor on growth response, matrix formation, and cytosolic free calcium of glomerular mesangial cells of spontaneously hypertensive and normotensive rats. Nephron. 1994;68(4):481–488. doi: 10.1159/000188311. [DOI] [PubMed] [Google Scholar]
  16. Hilderman R. H., Martin M., Zimmerman J. K., Pivorun E. B. Identification of a unique membrane receptor for adenosine 5',5"'-P1,P4-tetraphosphate. J Biol Chem. 1991 Apr 15;266(11):6915–6918. [PubMed] [Google Scholar]
  17. Hoyle C. H., Chapple C., Burnstock G. Isolated human bladder: evidence for an adenine dinucleotide acting on P2X-purinoceptors and for purinergic transmission. Eur J Pharmacol. 1989 Dec 12;174(1):115–118. doi: 10.1016/0014-2999(89)90881-9. [DOI] [PubMed] [Google Scholar]
  18. Isaka Y., Fujiwara Y., Ueda N., Kaneda Y., Kamada T., Imai E. Glomerulosclerosis induced by in vivo transfection of transforming growth factor-beta or platelet-derived growth factor gene into the rat kidney. J Clin Invest. 1993 Dec;92(6):2597–2601. doi: 10.1172/JCI116874. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Jaffer F. E., Knauss T. C., Poptic E., Abboud H. E. Endothelin stimulates PDGF secretion in cultured human mesangial cells. Kidney Int. 1990 Dec;38(6):1193–1198. doi: 10.1038/ki.1990.333. [DOI] [PubMed] [Google Scholar]
  20. MacKenzie I., Kirkpatrick K. A., Burnstock G. Comparative study of the actions of AP5A and alpha,beta-methylene ATP on nonadrenergic, noncholinergic neurogenic excitation in the guinea-pig vas deferens. Br J Pharmacol. 1988 Jul;94(3):699–706. doi: 10.1111/j.1476-5381.1988.tb11578.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Malam-Souley R., Campan M., Gadeau A. P., Desgranges C. Exogenous ATP induces a limited cell cycle progression of arterial smooth muscle cells. Am J Physiol. 1993 Apr;264(4 Pt 1):C783–C788. doi: 10.1152/ajpcell.1993.264.4.C783. [DOI] [PubMed] [Google Scholar]
  22. Nordhoff E., Ingendoh A., Cramer R., Overberg A., Stahl B., Karas M., Hillenkamp F., Crain P. F. Matrix-assisted laser desorption/ionization mass spectrometry of nucleic acids with wavelengths in the ultraviolet and infrared. Rapid Commun Mass Spectrom. 1992 Dec;6(12):771–776. doi: 10.1002/rcm.1290061212. [DOI] [PubMed] [Google Scholar]
  23. Olashaw N. E., Van Wyk J. J., Pledger W. J. Control of late G0/G1 progression and protein modification by SmC/IGF I. Am J Physiol. 1987 Oct;253(4 Pt 1):C575–C579. doi: 10.1152/ajpcell.1987.253.4.C575. [DOI] [PubMed] [Google Scholar]
  24. Osanai T., Dunn M. J. Phospholipase C responses in cells from spontaneously hypertensive rats. Hypertension. 1992 May;19(5):446–455. doi: 10.1161/01.hyp.19.5.446. [DOI] [PubMed] [Google Scholar]
  25. Pohl U., Ogilvie A., Lamontagne D., Busse R. Potent effects of AP3A and AP4A on coronary resistance and autacoid release of intact rabbit hearts. Am J Physiol. 1991 May;260(5 Pt 2):H1692–H1697. doi: 10.1152/ajpheart.1991.260.5.H1692. [DOI] [PubMed] [Google Scholar]
  26. Schlüter H., Offers E., Brüggemann G., van der Giet M., Tepel M., Nordhoff E., Karas M., Spieker C., Witzel H., Zidek W. Diadenosine phosphates and the physiological control of blood pressure. Nature. 1994 Jan 13;367(6459):186–188. doi: 10.1038/367186a0. [DOI] [PubMed] [Google Scholar]
  27. Schulze-Lohoff E., Zanner S., Ogilvie A., Sterzel R. B. Extracellular ATP stimulates proliferation of cultured mesangial cells via P2-purinergic receptors. Am J Physiol. 1992 Sep;263(3 Pt 2):F374–F383. doi: 10.1152/ajprenal.1992.263.3.F374. [DOI] [PubMed] [Google Scholar]
  28. Shultz P. J., DiCorleto P. E., Silver B. J., Abboud H. E. Mesangial cells express PDGF mRNAs and proliferate in response to PDGF. Am J Physiol. 1988 Oct;255(4 Pt 2):F674–F684. doi: 10.1152/ajprenal.1988.255.4.F674. [DOI] [PubMed] [Google Scholar]
  29. Silver B. J., Jaffer F. E., Abboud H. E. Platelet-derived growth factor synthesis in mesangial cells: induction by multiple peptide mitogens. Proc Natl Acad Sci U S A. 1989 Feb;86(3):1056–1060. doi: 10.1073/pnas.86.3.1056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Simonson M. S., Dunn M. J. Ca2+ signaling by distinct endothelin peptides in glomerular mesangial cells. Exp Cell Res. 1991 Jan;192(1):148–156. doi: 10.1016/0014-4827(91)90169-u. [DOI] [PubMed] [Google Scholar]
  31. Sterzel R. B., Schulze-Lohoff E., Marx M. Cytokines and mesangial cells. Kidney Int Suppl. 1993 Jan;39:S26–S31. [PubMed] [Google Scholar]
  32. Striker G. E., Striker L. J. Glomerular cell culture. Lab Invest. 1985 Aug;53(2):122–131. [PubMed] [Google Scholar]
  33. Veis J. H., Yamashita W., Liu Y. J., Ooi B. S. The biology of mesangial cells in glomerulonephritis. Proc Soc Exp Biol Med. 1990 Nov;195(2):160–167. doi: 10.3181/00379727-195-43129a. [DOI] [PubMed] [Google Scholar]
  34. Walker J., Lewis T. E., Pivorun E. P., Hilderman R. H. Activation of the mouse heart adenosine 5',5"'-P1-P4-tetraphosphate receptor. Biochemistry. 1993 Feb 9;32(5):1264–1269. doi: 10.1021/bi00056a010. [DOI] [PubMed] [Google Scholar]
  35. Weinmann-Dorsch C., Hedl A., Grummt I., Albert W., Ferdinand F. J., Friis R. R., Pierron G., Moll W., Grummt F. Drastic rise of intracellular adenosine(5')tetraphospho(5')adenosine correlates with onset of DNA synthesis in eukaryotic cells. Eur J Biochem. 1984 Jan 2;138(1):179–185. doi: 10.1111/j.1432-1033.1984.tb07897.x. [DOI] [PubMed] [Google Scholar]
  36. Wolthuis A., Boes A., Rodemann H. P., Grond J. Vasoactive agents affect growth and protein synthesis of cultured rat mesangial cells. Kidney Int. 1992 Jan;41(1):124–131. doi: 10.1038/ki.1992.16. [DOI] [PubMed] [Google Scholar]
  37. Yamaguchi N., Kodama M., Ueda K. Diadenosine tetraphosphate as a signal molecule linked with the functional state of rat liver. Gastroenterology. 1985 Oct;89(4):723–731. doi: 10.1016/0016-5085(85)90565-7. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES