Moerman E J, Thweatt R, Moerman A M, Jones R A, Goldstein S
Department of Medicine, University of Arkansas for Medical Sciences, Little Rock.
Exp Gerontol. 1993 Jul-Oct;28(4-5):361-70. 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 approximately 70-80%. These data indicate that IGFBP-3 may play an important role in the quiescent and senescent growth arrest of HDF.
在血清饥饿诱导的静止期以及血清再补充后的重新生长期间，与早期传代的正常（年轻）成纤维细胞培养物相比，晚期传代的正常（年老）成纤维细胞和来自沃纳综合征（WS）的早衰成纤维细胞培养物中，条件培养基中的细胞胰岛素样生长因子结合蛋白-3（IGFBP-3）mRNA和IGFBP-3水平始终较高。在衰老培养物中，IGFBP-3/IGF-II的摩尔比总是更高，并且维持着年老>WS>年轻人类二倍体成纤维细胞的等级关系。与用空表达载体（无cDNA）或用经273个碱基对（bp）缺失改变的IGFBP-3 cDNA转染的细胞相比，将正常全长IGFBP-3 cDNA在表达载体中转染到成纤维细胞中导致集落形成显著减少。以1:1或5:1的摩尔比向年老和年轻培养物中添加重组人IGFBP-3和IGF-I可抑制IGF-I介导的DNA合成约70-80%。这些数据表明，IGFBP-3可能在人皮肤成纤维细胞的静止和衰老生长停滞中起重要作用。
