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. 1991 Mar;2(3):219–227. doi: 10.1091/mbc.2.3.219

Intracellular signaling of transcription and secretion of type IV collagen after angiotensin II-induced cellular hypertrophy in cultured proximal tubular cells.

G Wolf 1, P D Killen 1, E G Neilson 1
PMCID: PMC361756  PMID: 1713478

Abstract

Physiologic concentrations of angiotensin II (AII) can induce cellular hypertrophy in murine proximal tubular epithelium (MCT cells). This response is characterized by an increase in cell size, new protein synthesis, and by the secretion of new basement membrane type IV collagen in the absence of cellular proliferation. The present study was undertaken to evaluate the second messengers of these AII-induced cellular events with special reference to the increase in type IV collagen secretion. In initial experiments we observed that pretreatment of MCT cells with agents that increase concentrations of intracellular cAMP, like forskolin, dibutyryl cAMP, and isobutyl-methyl-xanthine abolish AII-induced amino acid incorporation, but have no effect on control cells or on their proliferation. In addition, 10(-8) M AII significantly decreased the concentration of intracellular cAMP. Phorbolesters were without significant effect on the hypertrophy or proliferation of AII-stimulated MCT cells or their rested controls. The transfection of MCT cells with reporter genes containing regulatory elements for type IV collagen revealed that the stimulatory effects of AII on collagen type IV depend, at least to some extent, on an increase in gene transcription. Agents increasing intracellular cAMP concentrations inhibited the AII-induced increase in transcription and secretion of collagen type IV, but had no effect on MCT cells grown in media without AII. Our findings provide evidence that AII-induced changes in tubular epithelium leading to the secretion of type IV collagen are mediated by a decrease in intracellular cAMP.

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Selected References

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  1. Bergeron M., Hoang T. Adenosine and compensatory renal growth. Kidney Int. 1983 Apr;23(4):588–593. doi: 10.1038/ki.1983.62. [DOI] [PubMed] [Google Scholar]
  2. Bush G. L., Benson S. C. The effect of cyclic AMP on the accumulation of newly synthesized protein in the extracellular matrix of PFHR-9 teratocarcinoma cells. Connect Tissue Res. 1987;16(1):95–107. doi: 10.3109/03008208709001997. [DOI] [PubMed] [Google Scholar]
  3. Cogan M. G. Angiotensin II: a powerful controller of sodium transport in the early proximal tubule. Hypertension. 1990 May;15(5):451–458. doi: 10.1161/01.hyp.15.5.451. [DOI] [PubMed] [Google Scholar]
  4. Douglas J. G. Angiotensin receptor subtypes of the kidney cortex. Am J Physiol. 1987 Jul;253(1 Pt 2):F1–F7. doi: 10.1152/ajprenal.1987.253.1.F1. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Haverty T. P., Watanabe M., Neilson E. G., Kelly C. J. Protective modulation of class II MHC gene expression in tubular epithelium by target antigen-specific antibodies. Cell-surface directed down-regulation of transcription can influence susceptibility to murine tubulointerstitial nephritis. J Immunol. 1989 Aug 15;143(4):1133–1141. [PubMed] [Google Scholar]
  7. Killen P. D., Burbelo P. D., Martin G. R., Yamada Y. Characterization of the promoter for the alpha 1 (IV) collagen gene. DNA sequences within the first intron enhance transcription. J Biol Chem. 1988 Sep 5;263(25):12310–12314. [PubMed] [Google Scholar]
  8. Liu F. Y., Cogan M. G. Angiotensin II stimulates early proximal bicarbonate absorption in the rat by decreasing cyclic adenosine monophosphate. J Clin Invest. 1989 Jul;84(1):83–91. doi: 10.1172/JCI114174. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Liu F. Y., Cogan M. G. Angiotensin II stimulation of hydrogen ion secretion in the rat early proximal tubule. Modes of action, mechanism, and kinetics. J Clin Invest. 1988 Aug;82(2):601–607. doi: 10.1172/JCI113638. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Liu F. Y., Cogan M. G. Role of protein kinase C in proximal bicarbonate absorption and angiotensin signaling. Am J Physiol. 1990 Apr;258(4 Pt 2):F927–F933. doi: 10.1152/ajprenal.1990.258.4.F927. [DOI] [PubMed] [Google Scholar]
  11. Milanes C. L., Pernalete N., Starosta R., Perez-Gonzalez M., Paz-Martinez V., Bellorin-Font E. Altered response of adenylate cyclase to parathyroid hormone during compensatory renal growth. Kidney Int. 1989 Nov;36(5):802–809. doi: 10.1038/ki.1989.265. [DOI] [PubMed] [Google Scholar]
  12. Norman J., Badie-Dezfooly B., Nord E. P., Kurtz I., Schlosser J., Chaudhari A., Fine L. G. EGF-induced mitogenesis in proximal tubular cells: potentiation by angiotensin II. Am J Physiol. 1987 Aug;253(2 Pt 2):F299–F309. doi: 10.1152/ajprenal.1987.253.2.F299. [DOI] [PubMed] [Google Scholar]
  13. Rosenthal N. Identification of regulatory elements of cloned genes with functional assays. Methods Enzymol. 1987;152:704–720. doi: 10.1016/0076-6879(87)52075-4. [DOI] [PubMed] [Google Scholar]
  14. Schlondorff D., Weber H. Evidence for altered cyclic nucleotide metabolism during compensatory renal hypertrophy and neonatal kidney growth. Yale J Biol Med. 1978 May-Jun;51(3):387–392. [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Sekar M. C., Yang M., Meezan E., Pillion D. J. Angiotensin II and bradykinin stimulate phosphoinositide breakdown in intact rat kidney glomeruli but not in proximal tubules: glomerular response modulated by phorbol ester. Biochem Biophys Res Commun. 1990 Jan 15;166(1):373–379. doi: 10.1016/0006-291x(90)91955-r. [DOI] [PubMed] [Google Scholar]
  17. Strickland S., Smith K. K., Marotti K. R. Hormonal induction of differentiation in teratocarcinoma stem cells: generation of parietal endoderm by retinoic acid and dibutyryl cAMP. Cell. 1980 Sep;21(2):347–355. doi: 10.1016/0092-8674(80)90471-7. [DOI] [PubMed] [Google Scholar]
  18. Taubman M. B., Berk B. C., Izumo S., Tsuda T., Alexander R. W., Nadal-Ginard B. Angiotensin II induces c-fos mRNA in aortic smooth muscle. Role of Ca2+ mobilization and protein kinase C activation. J Biol Chem. 1989 Jan 5;264(1):526–530. [PubMed] [Google Scholar]
  19. Taylor S. S. cAMP-dependent protein kinase. Model for an enzyme family. J Biol Chem. 1989 May 25;264(15):8443–8446. [PubMed] [Google Scholar]
  20. Weinman E. J., Dubinsky W., Shenolikar S. Regulation of the renal Na+-H+ exchanger by protein phosphorylation. Kidney Int. 1989 Oct;36(4):519–525. doi: 10.1038/ki.1989.226. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Woodcock E. A., Johnston C. I. Inhibition of adenylate cyclase by angiotensin II in rat renal cortex. Endocrinology. 1982 Nov;111(5):1687–1691. doi: 10.1210/endo-111-5-1687. [DOI] [PubMed] [Google Scholar]

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