Senescent fibroblast facilitates re-epithelization and collagen deposition in radiation-induced skin injury through IL-33-mediated macrophage polarization.
J Transl Med
; 22(1): 176, 2024 02 18.
Article
en En
| MEDLINE
| ID: mdl-38369466
ABSTRACT
BACKGROUND:
The need for radiotherapy among the elderly rises with increasing life expectancy and a corresponding increase of elderly cancer patients. Radiation-induced skin injury is one of the most frequent adverse effects in radiotherapy patients, severely limiting their life quality. Re-epithelialization and collagen deposition have essential roles in the recovery of skin injuries induced by high doses of ionizing radiation. At the same time, radiation-induced senescent cells accumulate in irradiated tissues. However, the effects and mechanisms of senescent cells on re-epithelialization and collagen deposition in radiation-induced skin injury have not been fully elucidated.RESULTS:
Here, we identified a role for a population of senescent cells expressing p16 in promoting re-epithelialization and collagen deposition in radiation-induced skin injury. Targeted ablation of p16+ senescent cells or treatment with Senolytics resulted in the disruption of collagen structure and the retardation of epidermal coverage. By analyzing a publicly available single-cell sequencing dataset, we identified fibroblasts as a major contributor to the promotion of re-epithelialization and collagen deposition in senescent cells. Notably, our analysis of publicly available transcriptome sequencing data highlighted IL-33 as a key senescence-associated secretory phenotype produced by senescent fibroblasts. Neutralizing IL-33 significantly impedes the healing process. Finally, we found that the effect of IL-33 was partly due to the modulation of macrophage polarization.CONCLUSIONS:
In conclusion, our data suggested that senescent fibroblasts accumulated in radiation-induced skin injury sites participated in wound healing mainly by secreting IL-33. This secretion regulated the local immune microenvironment and macrophage polarization, thus emphasizing the importance of precise regulation of senescent cells in a phased manner.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Traumatismos por Radiación
/
Interleucina-33
Límite:
Aged
/
Humans
Idioma:
En
Revista:
J Transl Med
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Reino Unido