Shimamura Munehisa, Taniyama Yoshiaki, Nakagami Hironori, Katsuragi Naruto, Wakayama Kouji, Koriyama Hiroshi, Kurinami Hitomi, Tenma Akiko, Tomioka Hideki, Morishita Ryuichi
Division of Vascular Medicine and Epigenetics, Department of Child Development, United Graduate School of Child Development, Osaka University, Kanazawa University and Hamamatsu University School of Medicine, Osaka, Japan.
Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, Osaka, Japan.
Hypertens Res. 2014 Jun;37(6):494-9. doi: 10.1038/hr.2014.36. Epub 2014 Mar 20.
Periostin is an extracellular matrix glycoprotein and has various cellular effects. Previously, we demonstrated the neuroprotective effects of periostin during the acute stage of cerebral ischemia. However, its expression during the chronic stage remains unknown. Herein, we examined the expression of full-length periostin (periostin 1; Pn1) and its splicing variant lacking exon 17 (periostin 2; Pn2) during the 28 days following transient middle cerebral artery occlusion in mice. Real-time reverse transcription-PCR showed that the expression of Pn2 was dramatically upregulated between days 3 and 28, and the highest expression was observed on day 7. The expression of Pn1 was also increased, but delayed compared with Pn2. Immunohistochemistry showed that periostin was weakly expressed in reactive astrocytes in the peri-infarct region and in microglia/macrophages in infarct regions, on days 3 and 7. Periostin was also expressed around CD31-positive cells in both the peri-infarct and the sub-ventricular zone (SVZ) on days 3 and 7. SOX-2 positive cells, which are neural stem cells, also expressed periostin on day 7. The highest periostin immunoreactivity that occurred co-localized with collagen I and fibronectin in the peri-infarct region between days 7 and 28. Thus, the expression pattern of periostin mRNA was dependent on the splicing variant, and it continued to be expressed up to 28 days after cerebral ischemia. As periostin was expressed in various cells, such as reactive astrocytes/microglia, fibroblasts and neuronal progenitor cells, periostin might be associated with pathophysiology in post-ischemic inflammation and neurogenesis.
骨膜蛋白是一种细胞外基质糖蛋白，具有多种细胞效应。此前，我们证明了骨膜蛋白在脑缺血急性期的神经保护作用。然而，其在慢性期的表达情况仍不清楚。在此，我们检测了小鼠大脑中动脉短暂闭塞后28天内全长骨膜蛋白（骨膜蛋白1；Pn1）及其缺失外显子17的剪接变体（骨膜蛋白2；Pn2）的表达。实时逆转录聚合酶链反应显示，Pn2的表达在第3天至28天显著上调，在第7天观察到最高表达。Pn1的表达也增加，但比Pn2延迟。免疫组织化学显示，在第3天和第7天，骨膜蛋白在梗死周边区域的反应性星形胶质细胞以及梗死区域的小胶质细胞/巨噬细胞中弱表达。在第3天和第7天，骨膜蛋白也在梗死周边区域和脑室下区（SVZ）的CD31阳性细胞周围表达。作为神经干细胞的SOX-2阳性细胞在第7天也表达骨膜蛋白。在第7天至28天期间，梗死周边区域出现的最高骨膜蛋白免疫反应性与I型胶原和纤连蛋白共定位。因此，骨膜蛋白mRNA的表达模式取决于剪接变体，并且在脑缺血后持续表达至28天。由于骨膜蛋白在多种细胞中表达，如反应性星形胶质细胞/小胶质细胞、成纤维细胞和神经祖细胞，骨膜蛋白可能与缺血后炎症和神经发生的病理生理学相关。
