衰老
生物
肌成纤维细胞
表型
旁分泌信号
细胞生物学
转录组
细胞分化
信号转导
纤维化
基因表达
遗传学
基因
病理
受体
医学
作者
Irene López‐Antona,Constanza Contreras‐Jurado,Laura Luque‐Martín,Antonio Carpintero‐Leyva,Paula González‐Méndez,Ignacio Palmero
出处
期刊:Aging Cell
[Wiley]
日期:2022-03-09
卷期号:21 (4)
被引量:10
摘要
Cellular senescence is an antiproliferative response with a critical role in the control of cellular balance in diverse physiological and pathological settings. Here, we set to study the impact of senescence on the regulation of cell plasticity, focusing on the regulation of the myofibroblastic phenotype in primary fibroblasts. Myofibroblasts are contractile, highly fibrogenic cells with key roles in wound healing and fibrosis. Using cellular models of fibroblast senescence, we find a consistent loss of myofibroblastic markers and functional features upon senescence implementation. This phenotype can be transmitted in a paracrine manner, most likely through soluble secreted factors. A dynamic transcriptomic analysis during paracrine senescence confirmed the non-cell-autonomous transmission of this phenotype. Moreover, gene expression data combined with pharmacological and genetic manipulations of the major SASP signaling pathways suggest that the changes in myofibroblast phenotype are mainly mediated by the Notch/TGF-β axis, involving a dynamic switch in the TGF-β pathway. Our results reveal a novel link between senescence and myofibroblastic differentiation with potential implications in the physiological and pathological functions of myofibroblasts.
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