Transcriptomics

Dataset Information

0

Nintedanib induces senolytic effect via STAT3 inhibition


ABSTRACT: Selective removal of senescent cells, or the concept of senolytic therapy, has been proposed to be a potent strategy for overcoming age-related diseases and even reversing aging. We found that nintedanib, a tyrosine kinase inhibitor, selectively induced cell death in primary human diploid fibroblasts undergoing replicative senescence. Similar to ABT263, a well-known senolytic agent, nintedanib triggered intrinsic apoptosis in senescent cells. Additionally, at the concentration producing the senolytic effect, nintedanib arrested the cell cycle of nonsenescent cells in the G1 phase without cytotoxicity. Interestingly, compared with ABT263, nintedanib showed a different mode of activating caspase-9 in the intrinsic apoptotic pathway, in that nintedanib did not suppress the levels of Bcl-2 family proteins in senescent cells. In more detail, nintedanib suppressed the activation of the JAK2/STAT3 pathway, which caused drug-induced cell death in senescent cells. STAT3 knockdown in senescent cells also induced caspase activation. Moreover, nintedanib reduced the number of senescent cells stained based on senescence-associated β-galactosidase activity and airway resistance in a mouse model of bleomycin-induced lung fibrosis. Overall, we identified that nintedanib could be used as a new senolytic agent and that inhibiting STAT3 could be a potential approach for inducing selective cell death in senescent cells. Our findings will pave the way for expanding senolytic toolkits in response to various aging statuses and age-related diseases.

ORGANISM(S): Homo sapiens

PROVIDER: GSE210020 | GEO | 2022/09/06

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2024-12-17 | PXD054626 | Pride
| PRJNA863375 | ENA
2022-12-15 | GSE168037 | GEO
2024-03-23 | GSE245935 | GEO
2015-07-07 | E-GEOD-61677 | biostudies-arrayexpress
2024-03-20 | GSE231332 | GEO
2021-06-25 | GSE165468 | GEO
2021-06-25 | GSE165466 | GEO
2021-05-11 | GSE130382 | GEO
2023-01-06 | GSE157866 | GEO