Dermal fibroblasts from Down's syndrome patients share a cycloheximide-induced deficiency in collagen adhesion responses with normal aging cells.
Dermal fibroblasts from Down's syndrome patients share a cycloheximide-induced deficiency in collagen adhesion responses with normal aging cells.
复制标题
唐氏综合症患者的真皮成纤维细胞与正常衰老细胞一样，都存在放线菌酮诱导的胶原粘附反应缺陷。
DOI：
10.1016/0014-4827(90)90235-3
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发表时间：
1990
影响因子：
3.7
通讯作者：
Culp,LA
中科院分区：
文献类型：
--
作者：
Flickinger,KS;Culp,LA
Human skin fibroblasts from three different Down's syndrome patients (trisomy 21) of very different ages have been tested for their adhesion responses on tissue culture substrata coated with type I collagen, fibronectin (FN), and their combination after or during treatment of cells with cycloheximide to evaluate limitations in specific responses. It was shown previously thatin vitro-aged papillary and reticular dermal fibroblasts from normal individuals do not generate Factin stress fibers when pretreated with cycloheximide on collagen substrata but do so on FN substrata, a deficiency linked to limiting amounts/function of collagen-specific receptors in aging cells. In these studies, all three Down's fibroblast populations demonstrated a similar deficiency in stress fiber formation, evaluated by rhodamine-phalloidin staining, upon cycloheximide treatment at all passage levels. They remained competent for stress fiber formation on FN substrata and for reorganization of microtubule and intermediate filament networks on all substrata, demonstrating the specificity for the collagen matrix and for the F-actin cytoskeleton in this deficiency. The cycloheximide-induced deficiency could be readily reversed in all three cell populations by further incubation of cells in drug-free medium and, in some cases, by prior growth of cells in ascorbate-supplemented medium to stimulate collagen and possibly collagen receptor production. However, several pieces of evidence indicate that reduced amounts of FN and collagen synthesized by fibroblasts do not contribute to the cycloheximide-induced deficiency, including the inability to reverse the effect by treatment of cells with TGFβ. Several conclusions are suggested from these studies: (a) Down's dermal fibroblasts become deficient in collagen-specific receptor(s) upon cycloheximide treatment, which leads to altered transmembrane signaling and inability to reorganize F-actin into stress fibers; (b) Down's dermal fibroblasts at all passage levels have matrix adhesive phenotypes similar to those of aging fibroblasts from normal individuals; and (c) these studies provide further support for cells from Down's patients as a genetic model of aging in normal populations.
