| Gene name: | CCN1 |
| Aging type: | Accelerate |
| Aging characteristic: |
| Tissue type: | -- |
| Cell name: | MyoFibroblast |
| Gene ID: | 3491 |
| Category: | protein coding |
| Phenotype: | Liver disease |
| Experimental category: | L |
| PMID: | 23508104 |
| Experiment: | SA-β-gal activity assay |
| Description: | Numerous senescent cells were found surrounding the central veins in CCl4-treated Ccn1flox/flox mice as judged by the expression of senescence-associated β-galactosidase (SA-β-Gal) as a marker, but their numbers were reduced by ＞6 % in Ccn1△Hep mice ,indicating that CCN1 is critical for senescence. |
| Regulatory pathway: | RAC1-NOX1-ROS |
| R-AG-Pathway: | -- |
| Official symbol(s): | RAC1-NOX1-ROS1 |
| Pathway experiment: | RT-PCR//qRT-PCR//SA-β-gal activity assay//DHC//Knockdown |
| Pathway description: | CCN1 treatment specifically elevated Nox1 and Rac1 expression, but not expression of other Nox or Rac isoforms or of the Nox2 cofactor p47phox. Knockdown of either Nox1 or Rac1 by specific siRNAs inhibited CCN1-induced ROS and senescence as judged by cell proliferation and SA-β-Gal staining. Knockdown of Nox4, which is also expressed in fibroblasts, had no effect. Likewise, in activated PFs CCN1 induced ROS accumulation and senescence, which also required NOX-depen- dent ROS generation. These results show that CCN1 binds to integrin α6β1and induces cellular senescence through the RAC1-NOX1-ROS axis, leading to the expression of antifibrosis genes associated with the SASP to inhibit fibrosis. |
Annotation:
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