| Gene name: | SMAD4 |
| Aging type: | Prevent |
| Aging characteristic: |
| Tissue type: | -- |
| Cell name: | Fibroblast |
| Experiment: | qRT-PCR |
| Description: | Next, we assessed expression of cellular senescence and proliferative markers, including p16, p21, and Ki67. The mRNA levels of p16 and p21 were increased > 4-fold and > 5-fold, respectively, in mutant compared to control or SMAD4-WT cells. Consistent with this, expression of the proliferative marker Ki67 was substantially reduced in SMAD4-R496C mutant compared to control cells. Quantitative analysis of the cell cycle regulators, CDK2 and CDC25A, indicated reduced expression in SMAD4-R496C compared to controls, providing further evidence for repressed or halted cell cycle progression and enforcement of cellular senescence. |
| Regulatory pathway: | TGF-β/SMAD-IFNγ |
| R-AG-Pathway: | Activation |
| Pathway experiment: | qRT-PCR//SA-β-gal activity assay |
| Pathway description: | Consistent with this, the growth curve of Werner cells displayed an increased doubling time with passage compared to control normal fibroblasts. At passage 14, the population doubling time of Werner cells was markedly increased compared to corresponding controls, suggesting proliferative arrest and accelerated senescence of Werner cells, as described previously. Increased senescence of Werner cells was further supported by increased numbers of SA-beta positive cells and expression of IL-6, STAT1, and IFNγ. |
Annotation:
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