Proteolysis of insulin-like growth factor-binding protein-3 by human skin keratinocytes in culture in comparison to that in skin interstitial fluid: the role and regulation of components of the plasmin system

The Journal of Clinical Endocrinology and Metabolism
S XuJ M Holly

Abstract

Proteolysis of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) is an important determinant of IGF action on cells. We have investigated this in a human skin keratinocyte cell line HaCaT. Although these cells did not normally produce an active IGFBP-3 protease, addition of plasminogen resulted in a dose-dependent proteolysis of endogenous and exogenous IGFBP-3, producing fragments similar to those cleaved by skin interstitial fluid, but different from those generated by plasmin. Protease inhibitor profiles suggested the enzyme in the conditioned medium to be a calcium-dependent serine protease. Exogenous IGFBP-3 either inhibited or slightly stimulated IGF-I-induced cell proliferation when it was coincubated or preincubated with the cells, respectively. Both effects were attenuated in the presence of plasminogen. Preincubation of cells with IGF-I or long R3 IGF-I divergently changed plasminogen activator inhibitor-1 and -2 secretion, but only IGF-I blocked IGFBP-3 proteolysis. Such inhibition was also observed in a cell-free protease assay. IGF-I, however, had no effect on plasmin-induced IGFBP-3 degradation. Together, these data indicate that an IGFBP-3 protease similar to that in skin interstitial fluid is generate...Continue Reading

References

Jan 1, 1992·The British Journal of Dermatology·S M BurgeS A Cederholm-Williams
Oct 1, 1992·The Journal of Clinical Endocrinology and Metabolism·P CohenR G Rosenfeld
Jan 1, 1991·The Journal of Investigative Dermatology·E K NeelyR G Rosenfeld
Mar 1, 1988·The Journal of Cell Biology·P BoukampN E Fusenig
Jun 1, 1988·The Journal of Investigative Dermatology·K HashimotoP J Jensen
Nov 1, 1994·The Journal of Clinical Endocrinology and Metabolism·J A BatchG A Werther
Oct 1, 1995·The Journal of Clinical Endocrinology and Metabolism·S XuJ M Holly
Feb 1, 1995·Endocrine Reviews·J I Jones, D R Clemmons
Jun 1, 1996·The Journal of Endocrinology·M J Donnelly, J M Holly

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Citations

Nov 11, 2008·Journal of Mammary Gland Biology and Neoplasia·D J FlintG J Allan

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