旁分泌信号
纤维化
衰老
细胞外基质
细胞生物学
生物
成纤维细胞
真皮
下调和上调
真皮成纤维细胞
癌症研究
病理
细胞培养
医学
基因
解剖
受体
生物化学
遗传学
作者
Fariba Nosrati,Johannes Grillari,Mahnaz Azarnia,Mohammad Nabiuni,Reza Moghadasali,Latifeh Karimzadeh,Ingo Lämmermann
出处
期刊:Biogerontology
[Springer Nature]
日期:2023-01-17
卷期号:24 (2): 293-301
被引量:3
标识
DOI:10.1007/s10522-022-10013-y
摘要
Tissue fibrosis is associated with the aging process of most of our organs, and organ aging correlates with the chronic accumulation of senescent cells. Fibrosis occurs when fibroblasts proliferate and deposit pathological amounts of extracellular matrix (ECM), leading to progressive tissue scarring and organ dysfunction. Fibroblasts play a key role in fibrosis, especially in the skin where fibroblasts are the most abundant cell type in the dermis and are mainly responsible for the synthesis of ECM. This study aims to investigate how senescent fibroblasts and their secretome influence dermal fibrosis. Here we used human dermal fibroblasts (HDFs) treated with doxorubicin (doxo) to induce senescence. The senescent phenotype of these stress-induced premature senescent (SIPS) cells was confirmed with several markers. The expression of pro-fibrotic genes was quantified and finally, the impact of their secretome on the fibrotic response of non-senescent fibroblasts was assessed. Doxorubicin treatment, induced senescence in fibroblasts which has been confirmed with elevated senescence-associated β- galactosidase (SA-β-gal) activity, absence of BrdU incorporation, upregulation of p21, and loss of Lamin b1. Expression levels of the pro-fibrotic genes ACTA2 and FN1 increased in SIPS cells, but in contrast to studies using lung fibroblasts the secretome of these cells failed to induce a paracrine fibrotic response in non-senescent cells. In general, these results suggest that these senescent cells are potentially profibrotic, and their accumulation can trigger fibrosis in organs.
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