| Gene name: | IGFBP5 |
| Aging type: | Accelerate |
| Aging characteristic: |
| Tissue type: | -- |
| Cell name: | HUVEC |
| Experiment: | RT-PCR//Western blot//SA-β-gal activity assay//MTT assay//Flow cytometry |
| Description: | The levels of IGFBP-5 mRNA and protein in old cells were down-regulated by gene silencing using IGFBP-5 micro-RNA lentivirus. Transduction with IGFBP-5 micro-RNA lentivirus caused 65% decrease in IGFBP-5 levels. Repression of IGFBP-5 levels in old cells caused morphological changes similar to young cells and a decrease in SA-β-gal activity. Treatment of young cells with rhIGFBP-5 decreased cell proliferation both time- and dose-dependently. Furthermore, prolonged treatment with rhIGFBP-5 increased SA-β-gal staining and caused a characteristically enlarged and flattened morphology.To confirm that rhIGFBP-5–treated cells entered senescence-related cell cycle arrest, we analyzed DNA content by flow cytometry with PI staining. Most cells stimulated with rhIGFBP-5 for 2 d were arrested in G1 phase, which is one of the typical phenotypes in cellular senescence. |
| Target gene: | P53 |
| Official symbol(s): | P53 |
| R-AG-Target gene: | -- |
| Subcategory: | Unclear |
| Target gene experiment: | Knockdown//Western blot//MTT assay |
| Target gene description: | To further confirm that the p53 activation by IGFBP-5 might be mediated through DNA damage signaling, ATM level was down-regulated using siRNAs against ATM and the effects of IGFBP-5 overexpression were measured. Increases in p53 and phospho-p53 levels induced by IGFBP-5 up-regulation were repressed by knockdown of ATM. Furthermore, inhibition of cell proliferation induced by IGFBP-5 up-regulation was rescued by knockdown of ATM.These results suggested that IGFBP-5–induced cellular senescence is mediated by posttranslational modification of p53 such as phosphorylation and acetylation through DNA damage signaling. |
| Regulatory pathway: | -- |
| R-AG-Pathway: | -- |
| Pathway experiment: | -- |
| Pathway description: | -- |
Annotation:
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