Department of Neurosurgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima Red Cross Hospital, Tokushima, Japan.
World Neurosurg. 2012 Jul;78(1-2):114-21. doi: 10.1016/j.wneu.2011.05.052. Epub 2011 Nov 7.
Krüppel-like zinc-finger transcription factor 5 (KLF5), known as BTEB2 and IKLF, has several biological functions that involve cell proliferation, development, and apoptosis. In human cerebral aneurysms, macrophage infiltration is profoundly associated with growth and rupture, but the role of KLF5 remains unclear. We examined the significance of KLF5 expression in cerebral aneurysms.
Unruptured (n=15) and ruptured (n=12) aneurysms obtained at surgery or autopsy were divided into 3 size groups: small (<10 mm); large (≥10 mm but <25 mm); and giant (≥25 mm). Control samples comprised 5 cerebral arteries obtained from surgery or autopsy subjects. The expression of KLF5-, α-smooth muscle actin-, and KP-1 (macrophages) -positive cells were counted and compared between groups.
Media of control arteries was negative for KLF5. In the luminal layers, KLF5 in unruptured small aneurysm was also negative; KLF5 expression was higher in unruptured large/giant aneurysms than other groups (P<0.05). KP-1 expression in unruptured large/giant aneurysms, ruptured small aneurysms, and ruptured large/giant aneurysms was higher than in unruptured small aneurysms (P<0.05). In the unruptured large/giant aneurysms, KP-1-positive cells were lower than KLF5-positive cells. On the other hand, irrespective of size, KLF5 positivity tended to be lower than KP-1 in the luminal and abluminal layers of all ruptured aneurysms.
This represents the first documentation that KLF5 is highly expressed in large and giant unruptured aneurysms and that in ruptured aneurysmal wall KLF5 expression was scarce. These findings suggest that the KLF5 expression and macrophage infiltration play essential roles on aneurysmal growth or rupture.
Krüppel 样锌指转录因子 5(KLF5),又称为 BTEB2 和 IKLF,具有多种生物学功能,涉及细胞增殖、发育和凋亡。在人类脑动脉瘤中,巨噬细胞浸润与生长和破裂密切相关,但 KLF5 的作用尚不清楚。我们研究了 KLF5 表达在脑动脉瘤中的意义。
手术或尸检获得的未破裂(n=15)和破裂(n=12)动脉瘤分为 3 个大小组:小(<10mm);大(≥10mm 但<25mm);和巨大(≥25mm)。对照组包括 5 例手术或尸检患者的脑动脉。比较各组之间 KLF5、α-平滑肌肌动蛋白和 KP-1(巨噬细胞)阳性细胞的表达。
对照组动脉的中膜 KLF5 阴性。未破裂小动脉瘤的管腔层 KLF5 也为阴性;未破裂大/巨大动脉瘤的 KLF5 表达高于其他组(P<0.05)。未破裂大/巨大动脉瘤、破裂小动脉瘤和破裂大/巨大动脉瘤的 KP-1 表达高于未破裂小动脉瘤(P<0.05)。在未破裂大/巨大动脉瘤中,KP-1 阳性细胞低于 KLF5 阳性细胞。另一方面,无论大小,所有破裂动脉瘤的管腔和外膜层中 KLF5 阳性率均低于 KP-1 阳性率。
这是首次证明 KLF5 在未破裂大/巨大动脉瘤中高度表达,而在破裂动脉瘤壁中 KLF5 表达较少。这些发现表明,KLF5 表达和巨噬细胞浸润在动脉瘤生长或破裂中起重要作用。