流体剪切应力对人脐静脉内皮细胞Pim-1基因表达的影响

doi:10.13418/j.issn.1001-165x.2017.06.012

Abstract

Abstract:

Objective 　To investigate the effect of fluid shear stress(FSS) on the expression of Pim-1 in human umbilical vein endothelial cells (HUVECs) and the molecular mechanism of Pim-1 induced by FSS. Methods　HUVECs were isolated from the fresh umbilical cord of healthy mothers by 0.125% trypsin digestion. FSS under different time phase (1h, 4h, 6h) and at different magnitude (0.5Pa, 1.5Pa, 3.0Pa) were loaded by parallel plate flow chamber system. The expression of Pim-1 gene was detected by real-time RT-PCR at mRNA level and the levels of p-Akt and p-STAT3 were measured by Western Blot. The signaling inhibitors, Wortmannin (PI3K specific inhibitor), Deguelin (Akt inhibitor) and AG490 (JAK specific antagonist), were used to investigate possible signal transduction pathway.　Results　The expression of Pim-1 gene was significantly increased in HUVECs at 4h after 1.5Pa FSS. All FSS with different magnitude could increase Pim-1 expression, especially at high FSS(3.0Pa). Meanwhile, FSS can significantly activate the expression of p-Akt and p-STAT3. JAK inhibitor (AG490) significantly inhibited the expression of Pim-1, whereas PI3K inhibitor (Wortmannin) and Akt inhibitor (Deguelin) enhanced Pim-1 expression. Conclusions FSS can induce the expression of Pim-1 and its expression is closely related to the intensity of stimulation time and FSS. This effect may be mediated by JAK/STAT3 and PI3K/Akt signaling pathway.

Key words: Endothelial cells；　Pim-1；　Fluid shear stress(FSS)；　Gene expression ,

SUN Yu, WANG Xiao-bo, WANG Han-qin, YU Jian-xin. The effect of fluid shear stress on expression of Pim-1 in human umbilical vein endothelial cells [J]. Chinese Journal Of Clinical Anatomy, 2017, 35(6): 650-654.

References

[1] Baratchi S, Khoshmanesh K, Woodman OL, et al. Molecular Sensors of Blood Flow in Endothelial Cells[J]. Trends Mol Med, 2017, 23(9):850-868.
[2] Bachmann M, Möröy T. The serine/threonine kinase Pim-1[J]. Int J Biochem Cell Biol, 2005, 37(4):726–730.
[3] Walpen T, Peier M, Haas E, et al. Loss of pim1 imposes a hyperadhesive phenotype on endothelial cells[J]. Cell Physiol Biochem, 2012, 30(4): 1083-1096.
[4] Min X, Tang J, Wang Y, et al. PI3K-like kinases restrain Pim gene expression in endothelial cells[J]. J Huazhong Univ Sci Technolog Med Sci, 2012, 32(1): 17-23.
[5] Walpen T, Kalus I, Schwaller J, et al. Nuclear PIM1 confers resistance to rapamycin-impaired endothelial proliferation[J].Biochem Biophys Res Commun, 2012, 429(1-2):24-30.
[6] Chen M, Yi B, Zhu N, et al. Pim1 kinase promotes angiogenesis through phosphorylation of endothelial nitric oxide synthase at Ser-633[J]. Cardiovasc Res, 2016, 109(1): 141-150.
[7] Iwakura T, Mohri T, Hamatani T, et al. STAT3/Pim-1 signaling pathway plays a crucial role in endothelial differentiation of cardiac resident Sca-1+ cells both in vitro and in vivo[J]. J Mol Cell Cardiol, 2011, 51(2): 207-214.
[8] Chiu J J,Chien S. Effects of disturbed flow on vascular endothelium：pathophysiological basis and clinical perspectives[J]. Physiol Rev, 2011, 91(1): 327-387.
[9] Braso-Maristany F, Filosto S, Catchpole S, et al. PIM1 kinase regulates cell death, tumor growth and chemotherapy response in triple-negative breast cancer[J]. Nat Med, 2017, 23(6): 788.
[10]An N, Lin Y W, Mahajan S, et al. Pim1 serine/threonine kinase regulates the number and functions of murine hematopoietic stem cells[J]. Stem Cells, 2013, 31(6): 1202-1212.
[11]Mou S, Wang G, Ding D, et al. Expression and function of PIM kinases in osteosarcoma[J]. Int J Oncol, 2016, 49(5): 2116-2126.
[12]Tu M L, Wang H Q, Sun X D, et al. Pim-1 is up-regulated by shear stress and is involved in shear stress-induced proliferation of rat mesenchymal stem cells[J]. Life Sci, 2011, 88(5-6): 233-238.
[13]Liu P, Begley M, Michowski W, et al. Cell-cycle-regulated activation of Akt kinase by phosphorylation at its carboxyl terminus[J]. Nature, 2014, 508(7497): 541-545.
[14] Muraski J A, Rota M, Misao Y, et al. Pim-1 regulates cardiomyocyte survival downstream of Akt[J]. Nat Med, 2007, 13(12): 1467-1475.
[15]Cen B, Mahajan S, Wang W, et al. Elevation of receptor tyrosine kinases by small molecule AKT inhibitors in prostate cancer is mediated by Pim-1[J]. Cancer Res, 2013, 73(11): 3402-3411.

The effect of fluid shear stress on expression of Pim-1 in human umbilical vein endothelial cells

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Metrics

Comments

Recommended 0

[1]	Jiang Jianhong, Duan Renpeng, Li Xiaofeng. Application of three-dimensional visualization technology in the anatomical variations of hilar bile ducts in Chinese population [J]. Chinese Journal of Clinical Anatomy, 2024, 42(1): 1-4.
[2]	Guo Hongzhi, Wang Yu, Zhang Jiaqi, Liang Haibin, Ma Ziwei, Feng Wei, Wu You, Si Ziyi. Evaluation of placental vascular structure in preeclampsia by vascular casting combined with CT three-dimensional model [J]. Chinese Journal of Clinical Anatomy, 2024, 42(1): 5-10.
[3]	Li Jiawei, Zhang Jing, Li Canran, Lan Wenjie, Ji Qingyu, Guo Zhiyong, Zhang Yunfeng, Liu Qi, Chen Qingwei, Li Xiaohe. X-ray measurement of proximal femur anatomical parameters in Mongolian population [J]. Chinese Journal of Clinical Anatomy, 2024, 42(1): 11-16.
[4]	. Digital measurement and clinical significance of occipitocervical Angle and posterior occipitocervical Angle in children and adolescents [J]. Chinese Journal of Clinical Anatomy, 2024, 42(1): 17-20.
[5]	Li Wen, Yang Siyi, Huang Lei, Qing Jiwen, Jiang Songtao, Zhang Lei. Morphological characteristics and clinical significance of Lisfranc ligament based on MRI [J]. Chinese Journal of Clinical Anatomy, 2024, 42(1): 21-25.
[6]	Li Fanfan, Xu Yang, Wang Xiaoxu. Therapeutic effect of shikonin on the treatment of granuloma lobular mastitis in model rats by regulating Nrf2/HO-1 signaling pathway [J]. Chinese Journal of Clinical Anatomy, 2024, 42(1): 26-32.
[7]	Wang Xinghang, Ding Jiayuan, Li Fang, Bao Cuifen, Yan Lijing. Ginsenoside Rg1 reduces the inflammatory response of microglia after oxygen glucose deprivation/resupply by inhibiting the NLRP3 inflammasome pathway [J]. Chinese Journal of Clinical Anatomy, 2024, 42(1): 33-41.
[8]	Cheng Yingying, Wu Jianjun, Cai Haiyan , Jiao Xunwen, Ma Jiangbo, Ding Yinxiu. Activation and functional changes of astrocytes cultured in vitro under inflammatory stimulation [J]. Chinese Journal of Clinical Anatomy, 2024, 42(1): 42-46.
[9]	Qi Zhi, Yang Li, Jia Qiuye, Chen Haolun, Duan Zhaoda, Wu Chunyun. Edaravone regulates Sirt3 expression in lipopolysaccharide-activated microglia via MAPKs signaling pathway [J]. Chinese Journal of Clinical Anatomy, 2024, 42(1): 47-53.
[10]	Zhang Jingjing, Wang Hongxin. Protective effect of Baicalin on rats with pulmonary hypertension through PDGF/P38 MAPK signaling pathway [J]. Chinese Journal of Clinical Anatomy, 2024, 42(1): 54-58.
[11]	Yue Qin, Chen Rongli, Xiong Jingxi, Wang Tingyi, Cai Zhiheng, Yi Qiushi, Zeng Xinyi. Effect of Bletilla striata polysaccharides on the choke-area of cross-boundary flap in rats [J]. Chinese Journal of Clinical Anatomy, 2024, 42(1): 59-64.
[12]	Li Xiaoyu , Zhang Lei , Fu Lei , Li Dongbo , Wang Guoyou. Finite element study on the treatment of Sanders type II calcaneal fracture with three-step reduction method [J]. Chinese Journal of Clinical Anatomy, 2024, 42(1): 65-70.
[13]	Wu Yanfei, Ma Jianxiong, Lu Bin, Wang Ying, Bai Haohao, Jin Hongzhen, Ma Xinlong. Study on the correlation between the reconstruction of grayscale values using CT post-processing technology and the compressive strength of the endplate [J]. Chinese Journal of Clinical Anatomy, 2024, 42(1): 71-76.
[14]	Zhuang Wanqiang, Tang Yi, Luo Yonggang, Zhang Hui. An early and mid-term retrospective study of the effects of arthroscopy combined with high tibial osteotomy on patellar position and patellofemoral joint function [J]. Chinese Journal of Clinical Anatomy, 2024, 42(1): 77-82.
[15]	Luo Ying, Dou Weiyu, Wu Xiaohang, Chen Jingkun, Peng Changgui, Pan Jianying . Risk factors of postoperative complications of calcaneal fractures treated with hippocampal plate internal fixation through minimally invasive method [J]. Chinese Journal of Clinical Anatomy, 2024, 42(1): 83-88.