Col1a1+ perivascular cells in the brain are a source of retinoic acid following stroke.
Col1a1+ perivascular cells in the brain are a source of retinoic acid following stroke.
复制标题
DOI：
10.1186/s12868-016-0284-5
复制
发表时间：
2016-07-15
期刊：
影响因子：
2.4
通讯作者：
Siegenthaler JA
中科院分区：
文献类型：
--
作者：
Kelly KK;MacPherson AM;Grewal H;Strnad F;Jones JW;Yu J;Pierzchalski K;Kane MA;Herson PS;Siegenthaler JA
血管周围基质细胞（PSC）是最近鉴定的细胞类型，其在CNS血管周围空间内包含小百分比的血小板衍生生长因子受体-β+细胞。PSC在脑或脊髓损伤后被激活，数量增加并导致损伤部位内的纤维化瘢痕形成。除了纤维化，它们在病变核心的高密度使它们成为作用于病变部位附近神经细胞的潜在重要信号源。我们对PSC的发育分析（定义为胶原1a 1在成熟大脑中的表达）显示，PSC首先出现在出生后，可能起源于脑膜。PSC表达许多与脑膜成纤维细胞相同的标志物，包括视黄酸（RA）合成蛋白Raldh 1和Raldh 2的表达。使用局灶性脑缺血损伤模型诱导PSC活化和扩增，我们显示在病变核心中Raldh 1 +/Raldh 2 + PSC和Raldh 1+活化的巨噬细胞显著增加。我们发现，RA水平显着升高，在缺血半球和诱导信号在星形胶质细胞和神经元在梗死周围区域。这项研究强调了活化的非神经细胞的双重作用，其中PSC存款纤维化ECM蛋白，并且沿着巨噬细胞，作为RA的潜在重要来源，RA是一种有效的信号分子，可以在脑损伤后以神经保护的方式影响恢复事件。
Perivascular stromal cells (PSCs) are a recently identified cell type that comprises a small percentage of the platelet derived growth factor receptor-β+ cells within the CNS perivascular space. PSCs are activated following injury to the brain or spinal cord, expand in number and contribute to fibrotic scar formation within the injury site. Beyond fibrosis, their high density in the lesion core makes them a potential significant source of signals that act on neural cells adjacent to the lesion site. Our developmental analysis of PSCs, defined by expression of Collagen1a1 in the maturing brain, revealed that PSCs first appear postnatally and may originate from the meninges. PSCs express many of the same markers as meningeal fibroblasts, including expression of the retinoic acid (RA) synthesis proteins Raldh1 and Raldh2. Using a focal brain ischemia injury model to induce PSC activation and expansion, we show a substantial increase in Raldh1+/Raldh2+ PSCs and Raldh1+ activated macrophages in the lesion core. We find that RA levels are significantly elevated in the ischemic hemisphere and induce signaling in astrocytes and neurons in the peri-infarct region. This study highlights a dual role for activated, non-neural cells where PSCs deposit fibrotic ECM proteins and, along with macrophages, act as a potentially important source of RA, a potent signaling molecule that could influence recovery events in a neuroprotective fashion following brain injury.