SASP-induced macrophage dysfunction may contribute to accelerated senescent fibroblast accumulation in the dermis.
SASP-induced macrophage dysfunction may contribute to accelerated senescent fibroblast accumulation in the dermis.
复制标题
SASP 诱导的巨噬细胞功能障碍可能会加速真皮中衰老成纤维细胞的积累。
DOI：
10.1111/exd.14205
复制
发表时间：
2021
期刊：
影响因子：
3.6
通讯作者：
Akamatsu H.
中科院分区：
文献类型：
--
作者：
Ogata Y;Yamada T;Hasegawa S;Sanada A;Iwata Y;Arima M;Nakata S;Sugiura K;Akamatsu H.
最近，衰老相关分泌表型（SASP）受到越来越多的关注，这是一种衰老细胞分泌炎症细胞因子和基质金属蛋白酶（MMP）等分子的现象，因为它对周围组织有有害作用。众所周知，血液和肝脏中的衰老细胞会被巨噬细胞适当消耗。据报道，真皮中存在衰老细胞的积累，并被认为与皮肤老化有关。在本研究中，为了阐明真皮中衰老细胞的清除机制，我们重点关注巨噬细胞的功能。我们对衰老成纤维细胞和巨噬细胞的共培养实验揭示了一个两步清除机制：首先，巨噬细胞分泌的TNF-α诱导衰老成纤维细胞凋亡，然后，死亡细胞被巨噬细胞吞噬。此外，有人认为SASP因子抑制巨噬细胞清除衰老细胞的两个步骤。从这些发现来看，正常情况下真皮中的衰老细胞被认为是被巨噬细胞清除的，但是当衰老细胞由于氧化应激、紫外线或其他原因而过度积累时，SASP被认为可以抑制巨噬细胞依赖性清除功能，从而导致衰老细胞进一步积累。
Recently, increasing attention has been paid to senescence‐associated secretory phenotype (SASP), a phenomenon that senescent cells secrete molecules such as inflammatory cytokines and matrix metalloproteinases (MMPs), due to its noxious effects on the surrounding tissue. Senescent cells in the blood and liver are known to be properly depleted by macrophages. In the dermis, accumulation of senescent cells has been reported and is thought to be involved with skin ageing. In this study, to elucidate the clearance mechanism of senescent cells in the dermis, we focused on macrophage functions. Our co‐culture experiments of senescent fibroblasts and macrophages revealed a two‐step clearance mechanism: first, TNF‐α secreted from macrophages induces apoptosis in senescent fibroblasts, and then, dead cells are phagocytosed by macrophages. Furthermore, it was suggested that SASP factors suppress both of the two steps of the senescent cell clearance by macrophages. From these findings, normally senescent cells in the dermis are thought to be removed by macrophages, but when senescent cells are excessively accumulated owing to oxidative stress, ultraviolet (UV) ray or other reasons, SASP was suggested to suppress the macrophage‐dependent clearance functions and thereby cause further accumulation of senescent cells.