INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-3 ACCUMULATES TO HIGH-LEVELS IN CULTURE-MEDIUM OF SENESCENT AND QUIESCENT HUMAN FIBROBLASTS
INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-3 ACCUMULATES TO HIGH-LEVELS IN CULTURE-MEDIUM OF SENESCENT AND QUIESCENT HUMAN FIBROBLASTS
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DOI：
10.1073/pnas.88.21.9680
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发表时间：
1991-11-01
影响因子：
11.1
通讯作者：
BAXTER, RC
中科院分区：
文献类型：
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作者：
GOLDSTEIN, S;MOERMAN, EJ;BAXTER, RC
胰岛素样生长因子结合蛋白3（IGFBP-3）的mRNA水平始终较高，在衰老的正常人二倍体成纤维细胞（HDF）在晚期传代（老细胞）和过早衰老的HDF从一个受试者与沃纳综合征（WS）在血清消耗和补充的生长培养基和从稀疏到高密度抑制培养物的增殖过程中，与正常的早期传代（年轻）HDFs。然而，IGFBP-3蛋白积累到更高的水平，在条件培养基中的老细胞比在培养基中的WS和年轻细胞，在该顺序，在相同的条件下。胰岛素样生长因子I（IGF-I）在幼稚培养基或这三种细胞类型的条件培养基中均未检测到，而IGF-II在血清补充培养基中可检测到并保持相对恒定。因此，IGFBP-3/IGF-II的摩尔比在老年和WS细胞中始终较高，并且随着所有三种细胞类型由于血清消耗或高细胞密度而变得静止而大幅增加。这些数据与IGFBP-3蛋白在HDF衰老和静止生长停滞中的适应性或因果作用一致。
Insulin-like growth factor binding protein 3 (IGFBP-3) mRNA levels were consistently higher in both senescent normal human diploid fibroblasts (HDFs) at late passage (old cells) and prematurely senescent HDFs from a subject with Werner syndrome (WS) during serum depletion and repletion of growth medium and during proliferation from sparse to high-density inhibited cultures, compared to normal early-passage (young) HDFs. However, IGFBP-3 protein accumulated to higher levels in conditioned medium of old cells than in medium of WS and young cells, in that order, under the same conditions. Insulin-like growth factor I (IGF-I) was not detected in naive medium or in any of the media conditioned by these three cell types, whereas IGF-II was detectable in serum-repleted medium and remained relatively constant. Thus, molar ratios of IGFBP-3/IGF-II were consistently higher in old and WS cells and increased substantially as all three cell types became quiescent, due to either serum depletion or high cell density. These data are consistent with either an adaptive or a causal role for IGFBP-3 protein in the senescent and quiescent growth arrest of HDFs.