JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES) ›› 2015, Vol. 53 ›› Issue (4): 31-36.doi: 10.6040/j.issn.1671-7554.0.2014.775

Previous Articles     Next Articles

Involvement of canonical Wnt pathway in postischemic angiogenesis in a rat model of ischemic stroke

CHEN Haili, GU Jiaoyang, ZHANG Wenjing, YUAN Linran, ZHENG Juan, YUAN Zhongrui   

  1. Department of Pathophysiology, School of Medicine, Shandong University, Jinan 250012, Shandong, China
  • Received:2014-11-03 Revised:2015-01-05 Online:2015-04-10 Published:2015-04-10

PDF (PC)

219

Abstract: Objective To investigate the involvement of canonical Wnt pathway in postischemic angiogenesis by using a rat model of ischemic stroke. Methods A total of 50 normal male Wistar rats were randomly divided into 4 groups: Sham group (n=10), cerebral ischemia group (MCAO group, n=20), LiCl treated group (LiCl group, n=10) and DKK1 treated group (DKK1 group, n=10). Western blotting was used to detect the expression of the elements of canonical Wnt pathway. FITC-dextran was used to detect the vessel volume, and Laser Doppler was used to measure the local cerebral blood flow in ischemic penumbral. Results The expressions of β-catenin in both the nuclear fraction and the cytoplasmic fraction in MCAO group decreased at 1 day post-cerebral ischemia, compared with Sham group(P< 0.05). Nevertheless, the expressions of β-catenin in both the nuclear fraction and the cytoplasmic fraction at 7 day post-cerebral ischemia significantly increased (P< 0.05), and reached normal level at 14 day post-cerebral ischemia. Compared with MCAO group, the expressions of β-catenin in both the nuclear fraction and the cytoplasmic fraction LiCl group in were upregulated, accompanied with the elevated ratio of p-GSK-3β/GSK-3β, enhanced vessel volume and local cerebral blood flow in ischemic penumbral(P< 0.05). Compared with MCAO group, the expressions of β-catenin in DKK1 group in both the nuclear fraction and the cytoplasmic fraction were downregulated, accompanied with the decreased ratio of p-GSK-3β/GSK-3β, weakened vessel volume and local cerebral blood flow in ischemic penumbral(P< 0.05). Conclusion The canonical Wnt pathway might be involved in postischemic angiogenesis.

Key words: Canonical Wnt pathway, Rats, β-catenin, Angiogenesis, Ischemic stroke

CLC Number: 

  • R614.2
[1] Beck H, Plate KH. Angiogenesis after cerebral ischemia[J]. Acta Neuropathol, 2009, 117(5): 481-496.
[2] Li Y, Lu Z, Keogh CL, et al. Erythropoietin-induced neurovascular protection, angiogenesis, and cerebral blood flow restoration after focal ischemia in mice[J]. J Cereb Blood Flow Metab, 2007, 27(5): 1043-1054.
[3] MacDonald BT, Tamai K, He X. Wnt/beta-catenin signaling: components, mechanisms, and diseases[J]. Dev Cell, 2009, 17(1): 9-26.
[4] Daneman R, Agalliu D, Zhou L, et al. Wnt/beta-catenin signaling is required for CNS, but not non-CNS, angiogenesis[J]. Proc Natl Acad Sci U S A, 2009, 106(2): 641-646.
[5] Goodwin AM, Kitajewski J, D'Amore PA. Wnt1 and Wnt5a affect endothelial proliferation and capillary length; Wnt2 does not[J]. Growth Factors, 2007, 25(1): 25-32.
[6] Gherghe CM, Duan J, Gong J, et al. Wnt1 is a proangiogenic molecule,enhances human endothelial progenitor function,and increases blood flow boischemic limbs in a HGF-dependent manner[J]. FASEB J, 2011, 25(6):1836-1843.
[7] Xu J, Culman J, Blume A, et al. Chronic treatment witha low dose of lithium protects the brain againstischemic injury by reducing apoptotic death[J]. Stroke, 2003, 34(5):1287-1292.
[8] 李慧, 黄景阳, 陈海丽, 等. 脑缺血再灌注后大鼠海马Wnt7b的表达[J]. 山东大学学报:医学版, 2013, 51(2): 7-11. LI Hui, HUANG Jingyang, CHEN Haili, et al. Expression and location of Wnt7b in rat subgranular zone of hippocampus dentate gyrus after cerebral ischemia-reperfusion[J]. Journal of Shandong University: Health Sciences, 2013, 51(2): 7-11.
[9] Bederson JB, Pitts LH, Tsuji M, et al. Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic evaluation[J]. Stroke, 1986, 17(3):472-476.
[10] Dun Y, Li G, Yang Y, et al. Inhibition of the canonical Wnt pathway by Dickkopf-1 contributes to the neurodegeneration in 6-OHDA-lesioned rats[J]. Neurosci Lett, 2012, 525(2):83-88.
[11] Liu S, Liu W, Ding W, et al. Electron paramagnetic resonance-guided normobaric hyperoxia treatment protects the brain by maintaining penumbral oxygenation in a rat model of transient focal cerebral ischemia[J]. J Cereb Blood Flow Metab, 2006, 26(10):1274-1284.
[12] Daniels DL, Eklof Spink K, Weis WI. Beta-catenin: molecular plasticity and drug design[J]. Trends Biochem Sci, 2001, 26(11): 672-678.
[13] Clevers H, Nusse R. Wnt/β-catenin signaling and disease[J]. Cell, 2012, 149(6):1192-1205.
[14] Krupnik VE, Sharp JD, Jiang C, et al. Functional and structural diversity of the human Dickkopf gene family[J]. Gene, 1999, 238(2):301-313.
[15] Liu Z, Sun B, Qi L, et al. Dickkopf-1 expression is downregulated along colorectal adenoma-carcinoma sequence and correlates with reduced microvessel density and VEGF expression[J]. Histopathology, 2014, Jun 10. doi: 10.1111/his.12474.[Epub ahead of print].
[16] Cappuccio I, Calderone A, Busceti CL, et al. Induction of Dickkopf-1,a negative modulator of the Wnt pathway,is required for the development of ischemic neuronal death[J]. Neurosci, 2005, 25(10):2647-2657.
[17] Mastroiacovo F, Busceti CL, Biagioni F, et al. Induction of the Wnt antagonist, Dickkopf-1, contributes to the development of neuronal death in models of brain focal ischemia[J]. Cereb Blood Flow Metab, 2009, 29(2):264-276.
[18] Seifert-Held T, Pekar T, Gattringer T, et al. Circulating Dickkopf-1 in acute ischemic stroke and clinically stable cerebrovascular disease[J]. Atherosclerosis, 2011, 218(1):233-237.
[19] Morris DC, Zhang ZG, Wang Y, et al. Wnt expression in the adult rat subventricular zone after stroke[J]. Neurosci Lett, 2007, 418(2):170-174.
[20] Qu B, Liu BR, Du YJ, et al. Wnt/β-catenin signaling pathway may regulate the expression of angiogenic growth factors in hepatocellular carcinoma[J]. Oncol Lett, 2014, 7(4):1175-1178.
[21] Ren Z, Chen X, Cui G, et al. Nanosecond pulsed electric field inhibits cancer growth followed by alteration in expressions of NF-κB and Wnt/β-catenin signaling molecules[J]. PLoS One, 2013, 8(9): e74322. doi: 10.1371/journal.pone.0074322. eCollection 2013.
[22] Blankesteijn WM, van Gijn ME, Essers-Janssen YP, et al. Beta-catenin, an inducer of uncontrolled cell proliferation and migration in malignancies, is localized in the cytoplasm of vascular endothelium during neovascularization after myocardial infarction[J]. Am J Pathol, 2000, 157(3): 877-883.
[1] YU De-Xin, CAEI Ti-Gong, MA Xiang-Xing, ZHANG Xiao-Ming, LI Chuan-Fu. Angiogenesis and maturation of hepatocellular carcinoma [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2209, 47(6): 51-54.
[2] ZHU Lin, HU San-Yuan, ZHANG Guang-Yong, DING Xiang-Jiu. Protection of PGE2 against intestinal mucosa injuries in obstructed jaundice rats [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2209, 47(6): 12-.
[3] SUN Tao, ZHANG Dao-Lai, XIE Shan-Shan, WANG Yu-Zhuo, FENG Yu-Xin, XIN Hua. Effect of ethanol on expression of connexin 43 in primary culture of neural precursor cells [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2209, 47(6): 20-.
[4] ZHANG Dao-Lai, SUN Tao, XIE Shan-Shan, WANG Yu-Zhuo, ZHAO Ling, FENG Yu-Xin, XIN Hua. Developmental expression of NMDAR1 subunit on cultured cerebral cortical neurons of fetal rats in vitro [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2209, 47(6): 28-32.
[5] ZHANG Liang, XU Min, ZHUANG Xianghua, LOU Fuchen, LOU Nengjun, LÜ Li, GUO Wenjuan, ZHENG Fengjie, CHEN Shihong. An investigation of endoplasmic reticulum stress and apoptosis in diabetic peripheral neuropathy [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(8): 13-17.
[6] XIE Haibin, WU Qunzheng, LIU Shaozhuang, HUANG Xin, CHENG Yugang, HU Sanyuan, ZHANG Guangyong. Role of mitochondria-associated membranes in the improvement of insulin sensitivity in diabetic rats after sleeve gastrectomy [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(10): 36-40.
[7] CHEN Yikun, WANG Ketao, WANG Huayang, SHAO Qianqian, TAN Wanye, SONG Xiaobin, QU Xun, WEI Fengcai. Regulatory role of KIF4A in the expression of angiogenesis- associated factors of macrophages [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(1): 39-43.
[8] LI Fan, SHANG Wei. Clinical predictors of remote lesions for patients with acute ischemic stroke [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(6): 61-64.
[9] CHEN Yihui, LIU Xuewei, HOU Xuhao, SUN Qinfeng. Study of mouse alveolar bone defect reparation by dialdehyde bletilla striata glucomanna / hydroxypropyl chitosan / nano-nacre powder composited scaffolds [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(6): 7-11.
[10] LI Hongzhi, LIU Jing, SONG Yan, CHI Lingyi, LIU Yuguang. Role of liraglutide in the repair of spinal cord injury [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(4): 1-5.
[11] QU Lixin, SHI Xinghua, DU Yifeng. Relationship between circulating platelets microparticles and endothelial microparticls and prognosis in patients with acute ischemic stroke [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(12): 32-36.
[12] REN Baoxin, MA Yunfeng, LIU Dianwei, LI Zhuo, JIANG Yong. Effects of Wnt3a on neuronal autophagy and apoptosis in early brain injury after subarachnoid hemorrhage in rats [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(10): 11-15.
[13] CHEN Zhixin, WANG Ying, CAO Xinran, HEI Naihao, LI Junlong, DONG Bo, GUAN Guangju. Evaluation of the protective effect of AVE0991 on streptozotocin-induced diabetic nephropathy rats [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(10): 29-33.
[14] ZHANG Dongqing, WANG Yong, CHEN Shouzhen, ZHU Yaofeng, SHI Benkang. Changes on the expressions of alpha1-adrenergic receptor and nerve growth factor and their effects on urethral function in diabetic rats [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(9): 30-34.
[15] FENG Xiaoyu, ZHANG Hongmei, CHE Xuanqiang, KANG Donghong. Therapeutic effects of human osteoblast-stimulating factor on osteoporosis of ovariectomized rats [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(7): 8-12.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd