Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1990 Sep;137(3):541–552.

Glomerular lesions in mice transgenic for growth hormone and insulinlike growth factor-I. I. Relationship between increased glomerular size and mesangial sclerosis.

T Doi 1, L J Striker 1, C C Gibson 1, L Y Agodoa 1, R L Brinster 1, G E Striker 1
PMCID: PMC1877515  PMID: 2399934

Abstract

The glomeruli of mice transgenic for bovine growth hormone (GH mice) were disproportionately enlarged as a function of either kidney or body weight. Glomerular size correlated with mesangial sclerosis and the urine albumin/creatinine ratio. The glomerular lesions consisted of mesangial proliferation (4 to 5 weeks) followed by progressive mesangial sclerosis (19 weeks), resulting in complete glomerulosclerosis at 30 to 37 weeks. Albuminuria paralleled the glomerulosclerosis. In contrast, mice transgenic for insulinlike growth factor-I (IGF-I mice) did not develop glomerulosclerosis, even though glomerular size significantly increased. Glomerular hypertrophy, however, did not reach that in GH mice. These data suggest that high levels of circulating GH lead to a disproportionate increase in glomerular cellularity and volume, as well as glomerulosclerosis. This does not appear to be the result of high levels of circulating IGF-I stimulated by GH, as the serum IGF-I level in GH mice was lower than that in IGF-I mice.

Full text

PDF
541

Images in this article

542Figure 1
on p.542
544Figure 2
on p.544
544Figure 3
on p.544
550Figure 8
on p.550

Selected References

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

  1. Abboud H. E., Poptic E., DiCorleto P. Production of platelet-derived growth factorlike protein by rat mesangial cells in culture. J Clin Invest. 1987 Sep;80(3):675–683. doi: 10.1172/JCI113121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Adam C., Thoua Y., Ronco P., Verroust P., Tovey M., Morel-Maroger L. The effect of exogenous interferon: acceleration of autoimmune and renal diseases in (NZB/W) F1 mice. Clin Exp Immunol. 1980 May;40(2):373–382. [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Brenner B. M. Hemodynamically mediated glomerular injury and the progressive nature of kidney disease. Kidney Int. 1983 Apr;23(4):647–655. doi: 10.1038/ki.1983.72. [DOI] [PubMed] [Google Scholar]
  5. Chavers B. M., Bilous R. W., Ellis E. N., Steffes M. W., Mauer S. M. Glomerular lesions and urinary albumin excretion in type I diabetes without overt proteinuria. N Engl J Med. 1989 Apr 13;320(15):966–970. doi: 10.1056/NEJM198904133201503. [DOI] [PubMed] [Google Scholar]
  6. Christiansen J. S., Gammelgaard J., Orskov H., Andersen A. R., Telmer S., Parving H. H. Kidney function and size in normal subjects before and during growth hormone administration for one week. Eur J Clin Invest. 1981 Dec;11(6):487–490. doi: 10.1111/j.1365-2362.1981.tb02018.x. [DOI] [PubMed] [Google Scholar]
  7. Conti F. G., Striker L. J., Elliot S. J., Andreani D., Striker G. E. Synthesis and release of insulinlike growth factor I by mesangial cells in culture. Am J Physiol. 1988 Dec;255(6 Pt 2):F1214–F1219. doi: 10.1152/ajprenal.1988.255.6.F1214. [DOI] [PubMed] [Google Scholar]
  8. Conti F. G., Striker L. J., Lesniak M. A., MacKay K., Roth J., Striker G. E. Studies on binding and mitogenic effect of insulin and insulin-like growth factor I in glomerular mesangial cells. Endocrinology. 1988 Jun;122(6):2788–2795. doi: 10.1210/endo-122-6-2788. [DOI] [PubMed] [Google Scholar]
  9. Cook J. J., Haynes K. M., Werther G. A. Mitogenic effects of growth hormone in cultured human fibroblasts. Evidence for action via local insulin-like growth factor I production. J Clin Invest. 1988 Jan;81(1):206–212. doi: 10.1172/JCI113296. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Doi T., Striker L. J., Quaife C., Conti F. G., Palmiter R., Behringer R., Brinster R., Striker G. E. Progressive glomerulosclerosis develops in transgenic mice chronically expressing growth hormone and growth hormone releasing factor but not in those expressing insulinlike growth factor-1. Am J Pathol. 1988 Jun;131(3):398–403. [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. Fries J. W., Sandstrom D. J., Meyer T. W., Rennke H. G. Glomerular hypertrophy and epithelial cell injury modulate progressive glomerulosclerosis in the rat. Lab Invest. 1989 Feb;60(2):205–218. [PubMed] [Google Scholar]
  14. Gershoni J. M., Palade G. E. Protein blotting: principles and applications. Anal Biochem. 1983 May;131(1):1–15. doi: 10.1016/0003-2697(83)90128-8. [DOI] [PubMed] [Google Scholar]
  15. Hammer R. E., Brinster R. L., Palmiter R. D. Use of gene transfer to increase animal growth. Cold Spring Harb Symp Quant Biol. 1985;50:379–387. doi: 10.1101/sqb.1985.050.01.048. [DOI] [PubMed] [Google Scholar]
  16. Hirose K., Osterby R., Nozawa M., Gundersen H. J. Development of glomerular lesions in experimental long-term diabetes in the rat. Kidney Int. 1982 May;21(5):689–695. doi: 10.1038/ki.1982.82. [DOI] [PubMed] [Google Scholar]
  17. Hirschberg R., Kopple J. D. Evidence that insulin-like growth factor I increases renal plasma flow and glomerular filtration rate in fasted rats. J Clin Invest. 1989 Jan;83(1):326–330. doi: 10.1172/JCI113878. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Jansson J. O., Ekberg S., Hoath S. B., Beamer W. G., Frohman L. A. Growth hormone enhances hepatic epidermal growth factor receptor concentration in mice. J Clin Invest. 1988 Dec;82(6):1871–1876. doi: 10.1172/JCI113804. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Levey A. S., Perrone R. D., Madias N. E. Serum creatinine and renal function. Annu Rev Med. 1988;39:465–490. doi: 10.1146/annurev.me.39.020188.002341. [DOI] [PubMed] [Google Scholar]
  20. Lombet J. R., Adler S. G., Anderson P. S., Nast C. C., Olsen D. R., Glassock R. J. Sex vulnerability in the subtotal nephrectomy model of glomerulosclerosis in the rat. J Lab Clin Med. 1989 Jul;114(1):66–74. [PubMed] [Google Scholar]
  21. Lovett D. H., Ryan J. L., Sterzel R. B. A thymocyte-activating factor derived from glomerular mesangial cells. J Immunol. 1983 Apr;130(4):1796–1801. [PubMed] [Google Scholar]
  22. MacKay K., Striker L. J., Pinkert C. A., Brinster R. L., Striker G. E. Glomerulosclerosis and renal cysts in mice transgenic for the early region of SV40. Kidney Int. 1987 Dec;32(6):827–837. doi: 10.1038/ki.1987.283. [DOI] [PubMed] [Google Scholar]
  23. MacKay K., Striker L. J., Stauffer J. W., Agodoa L. Y., Striker G. E. Relationship of glomerular hypertrophy and sclerosis: studies in SV40 transgenic mice. Kidney Int. 1990 Feb;37(2):741–748. doi: 10.1038/ki.1990.41. [DOI] [PubMed] [Google Scholar]
  24. MacKay K., Striker L. J., Stauffer J. W., Doi T., Agodoa L. Y., Striker G. E. Transforming growth factor-beta. Murine glomerular receptors and responses of isolated glomerular cells. J Clin Invest. 1989 Apr;83(4):1160–1167. doi: 10.1172/JCI113996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Mathews L. S., Hammer R. E., Behringer R. R., D'Ercole A. J., Bell G. I., Brinster R. L., Palmiter R. D. Growth enhancement of transgenic mice expressing human insulin-like growth factor I. Endocrinology. 1988 Dec;123(6):2827–2833. doi: 10.1210/endo-123-6-2827. [DOI] [PubMed] [Google Scholar]
  26. Mathews L. S., Hammer R. E., Brinster R. L., Palmiter R. D. Expression of insulin-like growth factor I in transgenic mice with elevated levels of growth hormone is correlated with growth. Endocrinology. 1988 Jul;123(1):433–437. doi: 10.1210/endo-123-1-433. [DOI] [PubMed] [Google Scholar]
  27. Mauer S. M., Steffes M. W., Azar S., Sandberg S. K., Brown D. M. The effects of Goldblatt hypertension on development of the glomerular lesions of diabetes mellitus in the rat. Diabetes. 1978 Jul;27(7):738–744. doi: 10.2337/diab.27.7.738. [DOI] [PubMed] [Google Scholar]
  28. Morel-Maroger Striker L., Killen P. D., Chi E., Striker G. E. The composition of glomerulosclerosis. I. Studies in focal sclerosis, crescentic glomerulonephritis, and membranoproliferative glomerulonephritis. Lab Invest. 1984 Aug;51(2):181–192. [PubMed] [Google Scholar]
  29. Norstedt G., Palmiter R. Secretory rhythm of growth hormone regulates sexual differentiation of mouse liver. Cell. 1984 Apr;36(4):805–812. doi: 10.1016/0092-8674(84)90030-8. [DOI] [PubMed] [Google Scholar]
  30. Quaife C. J., Mathews L. S., Pinkert C. A., Hammer R. E., Brinster R. L., Palmiter R. D. Histopathology associated with elevated levels of growth hormone and insulin-like growth factor I in transgenic mice. Endocrinology. 1989 Jan;124(1):40–48. doi: 10.1210/endo-124-1-40. [DOI] [PubMed] [Google Scholar]
  31. Seaquist E. R., Goetz F. C., Rich S., Barbosa J. Familial clustering of diabetic kidney disease. Evidence for genetic susceptibility to diabetic nephropathy. N Engl J Med. 1989 May 4;320(18):1161–1165. doi: 10.1056/NEJM198905043201801. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Yoshida Y., Fogo A., Shiraga H., Glick A. D., Ichikawa I. Serial micropuncture analysis of single nephron function in subtotal renal ablation. Kidney Int. 1988 Apr;33(4):855–867. doi: 10.1038/ki.1988.77. [DOI] [PubMed] [Google Scholar]

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

RESOURCES