Skip to main content
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1992 Jan;140(1):95–107.

Angiotensin II stimulates the proliferation and biosynthesis of type I collagen in cultured murine mesangial cells.

G Wolf 1, U Haberstroh 1, E G Neilson 1
PMCID: PMC1886250  PMID: 1731533

Abstract

A murine mesangial cell line (MMC) was established from the glomeruli of SJL mice to study the influence of angiotensin II (ANG II) on their growth and function in a serum-free culture. Murine mesangial cells exhibit the phenotypic characteristics of mesangial cells, including staining for desmin, vimentin, Thy 1, and types I and IV collagen by immunofluorescence. The addition of daily doses of 10(-6) to 10(-11) mol/l ANG II to MMCs also induced their proliferation in serum-free media. This effect on growth was independent of the presence of insulin in the media, and was receptor mediated, because the specific ANG II-receptor antagonist DuP 753 abolished proliferative growth. Angiotensin II also stimulated mainly the biosynthesis of type I collagen in our MMCs. Transfection of MMCs with chimeric genes containing enhancer/promoter elements for alpha 2(I) and alpha 1(IV) collagens linked to a chloramphenicol acetyltransferase reporter demonstrated that the stimulatory effect of ANG II for type I depends, at least to some extent, on an increase in transcription. These findings indicate collectively that ANG II in serum-free cultures can be a paracrine catalyst for the growth and biosynthesis of type I collagen in mesangial cells.

Full text

PDF
95

Images in this article

Selected References

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

  1. Adler S., Striker L. J., Striker G. E., Perkinson D. T., Hibbert J., Couser W. G. Studies of progressive glomerular sclerosis in the rat. Am J Pathol. 1986 Jun;123(3):553–562. [PMC free article] [PubMed] [Google Scholar]
  2. Amenta P. S., Gay S., Vaheri A., Martinez-Hernandez A. The extracellular matrix is an integrated unit: ultrastructural localization of collagen types I, III, IV, V, VI, fibronectin, and laminin in human term placenta. Coll Relat Res. 1986 Jun;6(2):125–152. doi: 10.1016/s0174-173x(86)80021-8. [DOI] [PubMed] [Google Scholar]
  3. Anderson S., Diamond J. R., Karnovsky M. J., Brenner B. M. Mechanisms underlying transition from acute glomerular injury to late glomerular sclerosis in a rat model of nephrotic syndrome. J Clin Invest. 1988 Nov;82(5):1757–1768. doi: 10.1172/JCI113789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ardaillou N., Bellon G., Nivez M. P., Rakotoarison S., Ardaillou R. Quantification of collagen synthesis by cultured human glomerular cells. Biochim Biophys Acta. 1989 Jun 27;991(3):445–452. doi: 10.1016/0304-4165(89)90071-8. [DOI] [PubMed] [Google Scholar]
  5. Arnqvist H. J., Ballermann B. J., King G. L. Receptors for and effects of insulin and IGF-I in rat glomerular mesangial cells. Am J Physiol. 1988 Mar;254(3 Pt 1):C411–C416. doi: 10.1152/ajpcell.1988.254.3.C411. [DOI] [PubMed] [Google Scholar]
  6. Brennan D. C., Jevnikar A. M., Takei F., Reubin-Kelley V. E. Mesangial cell accessory functions: mediation by intercellular adhesion molecule-1. Kidney Int. 1990 Dec;38(6):1039–1046. doi: 10.1038/ki.1990.310. [DOI] [PubMed] [Google Scholar]
  7. Chiu A. T., McCall D. E., Aldrich P. E., Timmermans P. B. [3H]DUP 753, a highly potent and specific radioligand for the angiotensin II-1 receptor subtype. Biochem Biophys Res Commun. 1990 Nov 15;172(3):1195–1202. doi: 10.1016/0006-291x(90)91575-d. [DOI] [PubMed] [Google Scholar]
  8. Chiu A. T., McCall D. E., Price W. A., Wong P. C., Carini D. J., Duncia J. V., Wexler R. R., Yoo S. E., Johnson A. L., Timmermans P. B. Nonpeptide angiotensin II receptor antagonists. VII. Cellular and biochemical pharmacology of DuP 753, an orally active antihypertensive agent. J Pharmacol Exp Ther. 1990 Feb;252(2):711–718. [PubMed] [Google Scholar]
  9. Clayman M. D., Martinez-Hernandez A., Michaud L., Alper R., Mann R., Kefalides N. A., Neilson E. G. Isolation and characterization of the nephritogenic antigen producing anti-tubular basement membrane disease. J Exp Med. 1985 Feb 1;161(2):290–305. doi: 10.1084/jem.161.2.290. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Crawford J. M., Barton R. W. Thy-1 glycoprotein: structure, distribution, and ontogeny. Lab Invest. 1986 Feb;54(2):122–135. [PubMed] [Google Scholar]
  11. Downer G., Phan S. H., Wiggins R. C. Analysis of renal fibrosis in a rabbit model of crescentic nephritis. J Clin Invest. 1988 Sep;82(3):998–1006. doi: 10.1172/JCI113710. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fogo A., Ichikawa I. Evidence for the central role of glomerular growth promoters in the development of sclerosis. Semin Nephrol. 1989 Dec;9(4):329–342. [PubMed] [Google Scholar]
  13. Force T., Kyriakis J. M., Avruch J., Bonventre J. V. Endothelin, vasopressin, and angiotensin II enhance tyrosine phosphorylation by protein kinase C-dependent and -independent pathways in glomerular mesangial cells. J Biol Chem. 1991 Apr 5;266(10):6650–6656. [PubMed] [Google Scholar]
  14. 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]
  15. Gilbert S. F., Migeon B. R. D-valine as a selective agent for normal human and rodent epithelial cells in culture. Cell. 1975 May;5(1):11–17. doi: 10.1016/0092-8674(75)90086-0. [DOI] [PubMed] [Google Scholar]
  16. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Haralson M. A., Jacobson H. R., Hoover R. L. Collagen polymorphism in cultured rat kidney mesangial cells. Lab Invest. 1987 Nov;57(5):513–523. [PubMed] [Google Scholar]
  18. Haverty T. P., Kelly C. J., Hines W. H., Amenta P. S., Watanabe M., Harper R. A., Kefalides N. A., Neilson E. G. Characterization of a renal tubular epithelial cell line which secretes the autologous target antigen of autoimmune experimental interstitial nephritis. J Cell Biol. 1988 Oct;107(4):1359–1368. doi: 10.1083/jcb.107.4.1359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ishimura E., Sterzel R. B., Budde K., Kashgarian M. Formation of extracellular matrix by cultured rat mesangial cells. Am J Pathol. 1989 Apr;134(4):843–855. [PMC free article] [PubMed] [Google Scholar]
  20. Kashgarian M. Mesangium and glomerular disease. Lab Invest. 1985 Jun;52(6):569–571. [PubMed] [Google Scholar]
  21. Keane W. F., Raij L. Relationship among altered glomerular barrier permselectivity, angiotensin II, and mesangial uptake of macromolecules. Lab Invest. 1985 Jun;52(6):599–604. [PubMed] [Google Scholar]
  22. Kreisberg J. I. Insulin requirement for contraction of cultured rat glomerular mesangial cells in response to angiotensin II: possible role for insulin in modulating glomerular hemodynamics. Proc Natl Acad Sci U S A. 1982 Jul;79(13):4190–4192. doi: 10.1073/pnas.79.13.4190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kreisberg J. I., Karnovsky M. J. Glomerular cells in culture. Kidney Int. 1983 Mar;23(3):439–447. doi: 10.1038/ki.1983.40. [DOI] [PubMed] [Google Scholar]
  24. Menè P., Abboud H. E., Dunn M. J. Regulation of human mesangial cell growth in culture by thromboxane A2 and prostacyclin. Kidney Int. 1990 Aug;38(2):232–239. doi: 10.1038/ki.1990.191. [DOI] [PubMed] [Google Scholar]
  25. Mené P., Simonson M. S., Dunn M. J. Physiology of the mesangial cell. Physiol Rev. 1989 Oct;69(4):1347–1424. doi: 10.1152/physrev.1989.69.4.1347. [DOI] [PubMed] [Google Scholar]
  26. Merritt S. E., Killen P. D., Phan S. H., Wiggins R. C. Analysis of alpha 1 (I) procollagen alpha 1 (IV) collagen, and beta-actin mRNA in glomerulus and cortex of rabbits with experimental anti-glomerular basement membrane disease. Evidence for early extraglomerular collagen biosynthesis. Lab Invest. 1990 Dec;63(6):762–769. [PubMed] [Google Scholar]
  27. Ohyama K., Seyer J. M., Raghow R., Kang A. H. Extracellular matrix phenotype of rat mesangial cells in culture. Biosynthesis of collagen types I, III, IV, and V and a low molecular weight collagenous component and their regulation by dexamethasone. J Lab Clin Med. 1990 Aug;116(2):219–227. [PubMed] [Google Scholar]
  28. Pfeilschifter J., Bauer C. Pertussis toxin abolishes angiotensin II-induced phosphoinositide hydrolysis and prostaglandin synthesis in rat renal mesangial cells. Biochem J. 1986 May 15;236(1):289–294. doi: 10.1042/bj2360289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Re R. N., MacPhee A. A., Fallon J. T. Specific nuclear binding of angiotensin II by rat liver and spleen nuclei. Clin Sci (Lond) 1981 Dec;61 (Suppl 7):245s–247s. doi: 10.1042/cs061245s. [DOI] [PubMed] [Google Scholar]
  30. Re R., Parab M. Effect of angiotensin II on RNA synthesis by isolated nuclei. Life Sci. 1984 Feb 13;34(7):647–651. doi: 10.1016/0024-3205(84)90228-5. [DOI] [PubMed] [Google Scholar]
  31. Rosenblum N. D., Karnovsky M. J., Olsen B. R. Non-fibrillar collagenous proteins synthesized by rat mesangial cells. J Am Soc Nephrol. 1990 Nov;1(5):785–791. doi: 10.1681/ASN.V15785. [DOI] [PubMed] [Google Scholar]
  32. Rossi P., de Crombrugghe B. Identification of a cell-specific transcriptional enhancer in the first intron of the mouse alpha 2 (type I) collagen gene. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5590–5594. doi: 10.1073/pnas.84.16.5590. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Ruef C., Budde K., Lacy J., Northemann W., Baumann M., Sterzel R. B., Coleman D. L. Interleukin 6 is an autocrine growth factor for mesangial cells. Kidney Int. 1990 Aug;38(2):249–257. doi: 10.1038/ki.1990.193. [DOI] [PubMed] [Google Scholar]
  34. Scherberich J. E., Wolf G., Albers C., Nowack A., Stuckhardt C., Schoeppe W. Glomerular and tubular membrane antigens reflecting cellular adaptation in human renal failure. Kidney Int Suppl. 1989 Nov;27:S38–S51. [PubMed] [Google Scholar]
  35. Schlondorff D. The glomerular mesangial cell: an expanding role for a specialized pericyte. FASEB J. 1987 Oct;1(4):272–281. doi: 10.1096/fasebj.1.4.3308611. [DOI] [PubMed] [Google Scholar]
  36. Seikaly M. G., Arant B. S., Jr, Seney F. D., Jr Endogenous angiotensin concentrations in specific intrarenal fluid compartments of the rat. J Clin Invest. 1990 Oct;86(4):1352–1357. doi: 10.1172/JCI114846. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Stamenkovic I., Skalli O., Gabbiani G. Distribution of intermediate filament proteins in normal and diseased human glomeruli. Am J Pathol. 1986 Dec;125(3):465–475. [PMC free article] [PubMed] [Google Scholar]
  38. Striker G. E., Striker L. J. Glomerular cell culture. Lab Invest. 1985 Aug;53(2):122–131. [PubMed] [Google Scholar]
  39. Striker L. J., Doi T., Elliot S., Striker G. E. The contribution of glomerular mesangial cells to progressive glomerulosclerosis. Semin Nephrol. 1989 Dec;9(4):318–328. [PubMed] [Google Scholar]
  40. Tsuda T., Alexander R. W. Angiotensin II stimulates phosphorylation of nuclear lamins via a protein kinase C-dependent mechanism in cultured vascular smooth muscle cells. J Biol Chem. 1990 Jan 15;265(2):1165–1170. [PubMed] [Google Scholar]
  41. Ullian M. E., Linas S. L. Role of receptor cycling in the regulation of angiotensin II surface receptor number and angiotensin II uptake in rat vascular smooth muscle cells. J Clin Invest. 1989 Sep;84(3):840–846. doi: 10.1172/JCI114244. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Venkatachalam M. A., Kreisberg J. I. Agonist-induced isotonic contraction of cultured mesangial cells after multiple passage. Am J Physiol. 1985 Jul;249(1 Pt 1):C48–C55. doi: 10.1152/ajpcell.1985.249.1.C48. [DOI] [PubMed] [Google Scholar]
  43. Ward G. E., Kirschner M. W. Identification of cell cycle-regulated phosphorylation sites on nuclear lamin C. Cell. 1990 May 18;61(4):561–577. doi: 10.1016/0092-8674(90)90469-u. [DOI] [PubMed] [Google Scholar]
  44. Wolf G., Killen P. D., Neilson E. G. Cyclosporin A stimulates transcription and procollagen secretion in tubulointerstitial fibroblasts and proximal tubular cells. J Am Soc Nephrol. 1990 Dec;1(6):918–922. doi: 10.1681/ASN.V16918. [DOI] [PubMed] [Google Scholar]
  45. Wolf G., Killen P. D., Neilson E. G. Intracellular signaling of transcription and secretion of type IV collagen after angiotensin II-induced cellular hypertrophy in cultured proximal tubular cells. Cell Regul. 1991 Mar;2(3):219–227. doi: 10.1091/mbc.2.3.219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Wolf G., Kuncio G. S., Sun M. J., Neilson E. G. Expression of homeobox genes in a proximal tubular cell line derived from adult mice. Kidney Int. 1991 May;39(5):1027–1033. doi: 10.1038/ki.1991.130. [DOI] [PubMed] [Google Scholar]
  47. Wolf G., Neilson E. G. Angiotensin II induces cellular hypertrophy in cultured murine proximal tubular cells. Am J Physiol. 1990 Nov;259(5 Pt 2):F768–F777. doi: 10.1152/ajprenal.1990.259.5.F768. [DOI] [PubMed] [Google Scholar]
  48. Wolf G., Thaiss F., Scherberich J. E., Schoeppe W., Stahl R. A. Glomerular angiotensinase A in the rat: increase of enzyme activity following renal ablation. Kidney Int. 1990 Nov;38(5):862–868. doi: 10.1038/ki.1990.283. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES