| Gene name: | CCN1 |
| Aging type: | Accelerate |
| Aging characteristic: |
| Tissue type: | -- |
| Cell name: | BJ |
| Experiment: | BrdU assay//SA-β-gal activity assay//Immunostaining |
| Description: | Plication of CCN1 arrested cell proliferation within 3 days, as shown by stag-nant cell numbers and >50% decrease in 5-bromodeoxyuridine (BrdU)incorporation and Ki-67-positive cells when compared with bovine serum albumin (BSA)-treated controls ,CCN1-treated fibroblasts exhibited an enlarged and flattened cell morphology characteristic of senescent cells, and fourth, these cells expressed markers of senescence including SA-β-gal, p53 and p16INK4a. |
| Target gene: | P53//NOX1//P38MAPK//ERK |
| Official symbol(s): | P53//NOX1//P38MAPK//ERK |
| R-AG-Target gene: | Activation//Upregulation//Activation//Activation |
| Subcategory: | Unclear |
| Target gene experiment: | Western blot//Knockdown//RT-PCR |
| Target gene description: | Both p53 and p16INK4a proteins accumulated on CCN1 treatment, indicating their activation；CCN1 upregulated NOX1 expression in BJ cells,Knockdown of NOX1 by either of two shRNAs (#1 and #2) partially bypassed CCN1-induced growth arrest.Both kinases were activated by CCN1 in a biphasic manner (3 h and 24 h), and apocynin effectively abrogated ERK and p38 MAPK activation at both early and late phases |
| Regulatory pathway: | P16-PRB//INTEGRIN |
| R-AG-Pathway: | --//-- |
| Official symbol(s): | CDKN2A-RB1//ITGB |
| Pathway experiment: | Western blot//Knockdown//SA-β-gal activity assay |
| Pathway description: | Both p53 and p16INK4a proteins accumulated on CCN1 treatment, indicating their activation；silencing of p16INK4a by either expression of shRNA (shp16INK4a) or its suppressor Bmi-1 partially restored CCN1-induced growth suppression .Pretreatment of cells with either soluble heparin or a function-blocking monoclonal antibody against α6 integrin inhibited CCN1-induced SA-β-gal expression, whereas an antibody against αvβ3 integrin had no effect, indicating the involvement of α6β1 integrin and HSPGs. Furthermore, the addition of a peptide that competitively binds α6β1 integrin specifically blocked CCN1-induced senescence, whereas a peptide with a two-residue substitution (T1-mut) that abrogated binding of α6β1 integrin was ineffective . |
Annotation:
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