| Gene name: | SFRP1 |
| Aging type: | Accelerate |
| Aging characteristic: |
| Tissue type: | -- |
| Cell name: | IMR-90 |
| Experiment: | BrdU assay//Immunostaining//SA-β-gal activity assay//Cell morphological analysis//SAHF//RT-PCR |
| Description: | We then tested whether SFRP1 upregulation induces senescence. Lentiviral SFRP1 expression in IMR-9 cells caused striking proliferation arrest as determined by the lack of BrdU incorporation and Ki-67 staining , which was accompanied by senescence phenotypes including flat and enlarged morphology , senescence-associated β gal activity , senescence-associated heterochromatic foci, and induction of genes representing senescence-associated secretory phenotype. |
| Regulatory pathway: | WNT-β-CATENIN//RB//P53 |
| R-AG-Pathway: | Downregulation//Activation//-- |
| Official symbol(s): | Wnt-CTNNB1//retinoblastoma//TP53 |
| Pathway experiment: | Western blot//Luciferase reporter assay//Knockdown//SA-β-gal activity assay |
| Pathway description: | Lentiviral SFRP1 expression in IMR-90 cells resulted in reduced soluble βcatenin. Interestingly, etoposide treatment of IMR-90 cells, which stimulates SFRP1 secretion, also reduced soluble β-catenin levels.abolished etoposide-induced reduction of soluble β-catenin levels, suggesting that SFRP1 mediates the downregulation of Wnt signaling upon etoposide treatment. Suppression of Wnt signaling by SFRP1 and etoposide treatment was also verified by Wnt-responsive reporter assays: Wnt3 efficiently activated Super TOPFLASH reporter in IMR-90 cells, which was almost completely repressed by co-expression of SFRP1.Lentiviral SFRP1 expression in IMR-90 cells resulted in dephosphorylation of Rb, but the expression of p53 and a p53 transcriptional target, p21, remained unchanged, suggesting that SFRP1 activates the Rb pathway, but not the p53 pathway. Rb and p53 were efficiently silenced by corresponding shRNAs and upon SFRP1 expression, we observed significantly attenuated senescence induction in cells with Rb or p53 knock-down. This suggests that in addition to Rb, p53 is required for SFRP1-induced senescence even though SFRP1 does not activate the p53 pathway. |
Annotation:
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