Peng Yu-Tao, Shi Xiang-En, Li Zhi-Qiang, He Xin, Sun Yu-Ming
Department of Neurosurgery, Fu Xing Hospital, Capital Medical University, Beijing 100038, P.R. China.
Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing 100038, P.R. China.
Exp Ther Med. 2016 Dec;12(6):3905-3912. doi: 10.3892/etm.2016.3881. Epub 2016 Nov 7.
Particularly interesting Cys-His-rich protein (PINCH) has several biological functions in cancer development, invasion and metastasis in malignant cells, and the expression of PINCH is upregulated in several cancer types, including breast cancer, gastric adenocarcinoma and rectal cancer. However, the contribution of PINCH to human cerebral aneurysms remains largely unknown. Therefore, the significance of PINCH expression in cerebral aneurysm growth and rupture was examined in the present study. The protein expression levels of alpha-smooth muscle actin, osteopontin (OPN), matrix metalloproteinase (MMP) 9 and PINCH were evaluated using immunohistochemistry and western blot analyses. The results demonstrate that the protein expression levels of OPN, MMP9 and PINCH in the unruptured intracranial aneurysm (UA) and ruptured intracranial aneurysm (RA) groups were markedly higher than those of the control group, whereas OPN and PINCH expression levels were decreased in the RA group compared to those of the UA group. In addition, there was a strong correlation between PINCH and tumor size (=0.650 and P=0.0026), as well as between PINCH and OPN (=0.639 and P=0.0033) in the unruptured cerebral aneurysms. However, the correlation between PINCH and tumor size (=0.450 and P=0.1393) and between PINCH and OPN (=0.366 and P=0.2426) revealed no obvious difference in the ruptured cerebral aneurysms. In conclusion, PINCH was highly expressed in the UAs, which may be a critical factor for preventing aneurysmal rupture. Moreover, PINCH may facilitate intracranial aneurysm progression, at least partially, through the activation of extracellular signal-regulated kinase signaling and the suppression of c-Jun N-terminal kinase signaling.
特别有趣的富含半胱氨酸-组氨酸的蛋白质（PINCH）在恶性细胞的癌症发展、侵袭和转移中具有多种生物学功能，并且PINCH的表达在包括乳腺癌、胃腺癌和直肠癌在内的几种癌症类型中上调。然而，PINCH对人脑动脉瘤的作用在很大程度上仍然未知。因此，本研究检测了PINCH表达在脑动脉瘤生长和破裂中的意义。使用免疫组织化学和蛋白质印迹分析评估了α-平滑肌肌动蛋白、骨桥蛋白（OPN）、基质金属蛋白酶（MMP）9和PINCH的蛋白质表达水平。结果表明，未破裂颅内动脉瘤（UA）组和破裂颅内动脉瘤（RA）组中OPN、MMP9和PINCH的蛋白质表达水平明显高于对照组，而与UA组相比，RA组中OPN和PINCH的表达水平降低。此外，在未破裂脑动脉瘤中，PINCH与肿瘤大小之间存在强相关性（=0.650，P=0.0026），以及PINCH与OPN之间存在强相关性（=0.639，P=0.0033）。然而，在破裂脑动脉瘤中，PINCH与肿瘤大小之间的相关性（=0.450，P=0.1393）以及PINCH与OPN之间的相关性（=0.366，P=0.2426）没有明显差异。总之，PINCH在未破裂颅内动脉瘤中高表达，这可能是预防动脉瘤破裂的关键因素。此外，PINCH可能至少部分地通过激活细胞外信号调节激酶信号传导和抑制c-Jun氨基末端激酶信号传导来促进颅内动脉瘤进展。
