Insulin-like growth factor binding protein-5 and senescence of human fibroblasts
| Autor: | Sung-lin Tsai, 蔡松霖 |
|---|---|
| Rok vydání: | 2007 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 95 The function of insulin-like growth factor binding protein-5 ( IGFBP-5 ) in human fibroblasts is not clear. Using microarray technique, we have previous observed that the IGFBP-5 mRNA of senescent fibroblasts was significantly increased. To define the relationship between IGFBP-5 and senescence of human fibroblasts, IGF-I and IGFBP-5 were exogenously added to young and senescent cells to examine their effects on growth by MTT assay. Growth of both young and senescent cells could be stimulated by exogenously added IGF-I. Exogenously added IGFBP-5 stimulated growth of young cells by 25%; in contrast, it had no significant effect on senescent cells. Addition of IGF further enhanced the growth of these cells. Co-treatment of 50 ng/ml IGF and 50 ng/ml IGFBP-5 stimulated growth of young cells by 75%. IGFBP-5 mRNA increased during cellular senescence and confluence as evidence by the result of RT-PCR and Q-PCR. However, the level of IGFBP-5 protein decreased under these conditions. H2O2-mediated premature senescence was associated with reduction of IGFBP-5 protein. Transduction of IGFBP-5 gene increased the protein expression of IGFBP-5 only in young cells, but not in senescent cells. These findings suggest that IGFBP-5 can stimulate the growth of human fibroblasts, and augment the stimulating effect of IGF. The discordant expression of IGFBP-5 at mRNA and protein levels during senescence suggests involvement of additional regulatory mechanisms. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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