Riew Tae-Ryong, Choi Jeong-Heon, Kim Hong Lim, Jin Xuyan, Lee Mun-Yong
Department of Anatomy, Catholic Neuroscience Institute, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Integrative Research Support Center, Laboratory of Electron Microscope, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Front Mol Neurosci. 2018 Nov 5;11:402. doi: 10.3389/fnmol.2018.00402. eCollection 2018.
Perivascular cells expressing platelet-derived growth factor receptor beta (PDGFR-β) have recently been implicated in fibrotic scar formation after acute brain injury, but their precise identity and detailed morphological characteristics remain elusive. This study sought to characterize and define the cellular phenotype of vascular-associated cells expressing PDGFR-β in the striatum of rats treated with the mitochondrial toxin 3-nitropropionic acid (3-NP). In the control striatum, PDGFR-β-positive cells were invariably localized on the abluminal side of smooth muscle cells of larger caliber vessels, and demonstrated morphological features typical of perivascular fibroblasts. PDGFR-β expression increased and expanded to almost all vessels, including microvessels in the lesion core, at 7 days after 3-NP injection. The cells expressing PDGFR-β had ultrastructural features of fibroblasts undergoing active collagen synthesis: large euchromatic nuclei with a prominent nucleolus, well-developed rough endoplasmic reticulum (rER) with dilated cisterns and extracellular collagen fibrils. By 14 days, PDGFR-β-positive cells had somata located at a distance from the vasculature, and their highly ramified, slender processes overlapped with those from other cells, thus forming a plexus of processes in the extravascular space of the lesion core. In addition, their ultrastructural morphology and spatial correlation with activated microglia/macrophages were elaborated by three-dimensional reconstruction. Using a correlative light- and electron-microscopy technique, we found that the intermediate filament proteins nestin and vimentin were induced in PDGFRβ-positive fibroblasts in the lesion core. Collectively, our data suggest that perivascular PDGFR-β-positive fibroblasts are distinct from other vascular cell types, including pericytes and contribute to fibrotic scar formation in the lesion core after acute brain injury. Nestin and vimentin play critical roles in the structural dynamics of these reactive fibroblasts.
表达血小板衍生生长因子受体β（PDGFR-β）的血管周围细胞最近被认为与急性脑损伤后的纤维化瘢痕形成有关，但其确切身份和详细形态特征仍不清楚。本研究旨在表征和定义在用线粒体毒素3-硝基丙酸（3-NP）处理的大鼠纹状体中表达PDGFR-β的血管相关细胞的细胞表型。在对照纹状体中，PDGFR-β阳性细胞始终位于较大口径血管平滑肌细胞的无腔侧，并表现出血管周围成纤维细胞的典型形态特征。3-NP注射后7天，PDGFR-β表达增加并扩展到几乎所有血管，包括病变核心的微血管。表达PDGFR-β的细胞具有正在进行活跃胶原合成的成纤维细胞的超微结构特征：大的常染色质核，有明显的核仁，发达的粗面内质网（rER），其池扩张并有细胞外胶原纤维。到14天时，PDGFR-β阳性细胞的胞体位于远离血管的位置，其高度分支的细长突起与其他细胞的突起重叠，从而在病变核心的血管外空间形成一个突起丛。此外，通过三维重建阐述了它们的超微结构形态以及与活化的小胶质细胞/巨噬细胞的空间相关性。使用相关光镜和电镜技术，我们发现病变核心中PDGFRβ阳性成纤维细胞中诱导了中间丝蛋白巢蛋白和波形蛋白。总体而言，我们的数据表明血管周围PDGFR-β阳性成纤维细胞与其他血管细胞类型（包括周细胞）不同，并在急性脑损伤后病变核心的纤维化瘢痕形成中起作用。巢蛋白和波形蛋白在这些反应性成纤维细胞的结构动力学中起关键作用。
