Overexpression of insulin-like growth factor binding protein-3 by senescent human fibroblasts: attenuation of the mitogenic response to IGF-I

Experimental Cell Research
V G GrigorievS Goldstein

Abstract

We have previously demonstrated that senescent human diploid fibroblasts (HDF) produce large amounts of IGF-binding protein-3 (IGFBP-3) in comparison to early-passage vigorously proliferative HDF. In order to determine whether this excess IGFBP-3 accumulation plays a role in the observed attenuation of DNA synthesis in senescent HDF, we examined the response of these cells to IGF-I and two IGF-I functional analogs, [QAYL]IGF-I and insulin, both of which have extremely low binding affinity for IGFBP-3 but which exert their mitogenic effect via the IGF-I plasma membrane receptor. Senescent HDF showed an increased sensitivity of DNA synthetic response to [QAYL]IGF-I and insulin compared to IGF-I. IGF binding activity was significantly higher in conditioned medium of senescent HDF than the medium of young HDF, and virtually all of this enhanced binding capacity could be accounted for by IGFBP-3. Addition of recombinant IGFBP-3 to young cells at a constant molar ratio of 1:1 with respect to IGF-I significantly attenuated the response to IGF-I and abolished the response at a 2:1 molar ratio. These data indicate that IGFBP-3 accumulated in medium of senescent HDF can bind and sequester IGFs when present in molar excess and thereby acc...Continue Reading

Citations

Oct 8, 2005·American Journal of Physiology. Gastrointestinal and Liver Physiology·Munenori TakaokaHiroshi Nakagawa
Oct 7, 2009·Respiratory Research·Julia A PaxsonAndrew M Hoffman
Jan 31, 2006·BMC Developmental Biology·Mark R Corkins, Michael J Fillenwarth
Aug 1, 1997·Endocrine·C A Conover
Jan 6, 2006·European Journal of Gastroenterology & Hepatology·Katherine M GetliffeChuka U Nwokolo
Dec 13, 2003·Endocrine Reviews·Stephanie R EdmondsonChristopher J Wraight
Jan 1, 1996·Experimental Gerontology·V G GrigorievS Goldstein
Jan 1, 1996·Experimental Gerontology·B Lecka-CzernikS Goldstein

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