Insulin-like growth factor binding protein-3 is overexpressed in senescent and quiescent human fibroblasts

• Published in: Experimental gerontology 1993-07, Vol.28 (4), p.361-370
• Main Authors: Moerman, Elena J., Thweatt, Ray, Moerman, Andrea M., Jones, Richard A., Goldstein, Samuel
• Format: Article
• Language: English
• Subjects: aging; Aging - metabolism; Biological and medical sciences; Carrier Proteins - biosynthesis; Carrier Proteins - genetics; Cell Division - physiology; cell proliferation; Cells, Cultured; Cellular Senescence - physiology; Child; Culture Media, Conditioned; Development. Metamorphosis. Moult. Ageing; DNA - biosynthesis; Fibroblasts - metabolism; Fibroblasts - pathology; Fundamental and applied biological sciences. Psychology; growth inhibition; Growth Inhibitors - biosynthesis; Growth Inhibitors - genetics; Humans; IGFBP-3; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I - biosynthesis; Insulin-Like Growth Factor II - biosynthesis; Male; Middle Aged; RNA, Messenger - biosynthesis; Time Factors; Transfection; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Werner syndrome; Werner Syndrome - metabolism; Werner Syndrome - pathology
• ISSN: 0531-5565; 1873-6815
• DOI: 10.1016/0531-5565(93)90063-J

Cellular insulin-like growth factor binding protein-3 (IGFBP-3) mRNA and IGFBP-3 levels in conditioned medium were consistently higher in cultures of late passage normal (old) fibroblasts and prematurely senescent fibroblasts derived from Werner syndrome (WS) during quiescence induced by serum depletion and during the renewed growth ensuing after serum repletion, compared to cultures of early passage normal (young) fibroblasts. Molar ratios of IGFBP-3/IGF-II were always higher in senescent cultures and maintained a hierarchy of old > WS > young human diploid fibroblasts. Transfection into fibroblasts of the normal full-length IGFBP-3 cDNA in an expression vector resulted in a significant reduction in colony formation compared to cells transfected with an empty expression vector (no cDNA) or with IGFBP-3 cDNA altered by a 273 base pair (bp) deletion. Addition to old and young cultures of recombinant human IGFBP-3 and IGF-I at 1:1 or 5:1 molar ratios inhibited IGF-I-mediated DNA synthesis by ≈ 70–80%. These data indicate that IGFBP-3 may play an important role in the quiescent and senescent growth arrest of HDF.