|
|
- 2018
ERK5抑制剂对巨噬细胞胞葬作用及ProS、Axl表达的影响
|
Abstract:
摘要 目的： 观察ERK5抑制剂对巨噬细胞胞葬作用及相关信号分子ProS、Axl表达的影响.方法: 体外常规培养RAW264.7巨噬细胞,并用ERK5抑制剂(XMD8-92和ERK5-IN-1)干预细胞,实验分为正常对照组、XMD8-92组和ERK5-IN-1组;流式细胞仪检测巨噬细胞的胞葬率,RT-qPCR和Western blot法检测巨噬细胞ProS和Axl的mRNA和蛋白的表达.结果: 与正常对照组相比,XMD8-92组和ERK5-IN-1组巨噬细胞胞葬率下降(P<0.05),ProS和Axl的mRNA和蛋白的表达水平下调(P<0.05).结论: ERK5抑制剂可以抑制巨噬细胞的胞葬作用,下调胞葬作用相关信号分子ProS和Axl的mRNA和蛋白的表达,提示ERK5激酶的失活可能通过下调ProS、Axl的表达导致巨噬细胞胞葬作用受损.
| [1] | GENG K, KUMAR S, KIMANI S G, et al.Requirement of gamma-carboxyglutamic acid modification and phosphatidylserine binding for the activation of Tyro3, Axl, and Mertk receptors by growth arrest-specific 6[J].Front Immunol,2017,8:1521. |
| [2] | SUN Y, LIU W Z, LIU T, et al.Signaling pathway of MAPK/ERK in cell proliferation, differentiation, migration, senescence and apoptosis[J].J Recept Signal Transduct Res,2015,35(6):600-604. |
| [3] | 王建茹, 刘萍. 胞外信号调节激酶5与心血管疾病关系的研究进展[J].中国老年学杂志,2016,36(13): 3315-3317. |
| [4] | UDERHARDT S, HERRMANN M, OSKOLKOVA O V, et al.12/15-lipoxygenase orchestrates the clearance of apoptotic cells and maintains immunologic tolerance[J].Immunity, 2012,36(5):834-846. |
| [5] | 陈朱波, 曹雪涛. 流式细胞术:原理、操作及应用[M].2版.北京:科学出版社,2014:166-167. |
| [6] | DE CATHELINEAU A M, HENSON P M. The final step in programmed cell death: phagocytes carry apoptotic cells to the grave[J].Essays in Biochemistry,2002,39(4):105-117. |
| [7] | TRAHTEMBERG U, MEVORACH D.Apoptotic cells induced signaling for immune homeostasis in macrophages and dendritic cells[J].Front Immunol,2017,8:1356. |
| [8] | WANG J R, LIU P.Advances in the Research of Relationship between ERK5 and Cardiovascular Disease[J].Chinese Journal of Gerontology,2016,36(13): 3315-3317. |
| [9] | HEO K S, CUSHMAN H J, AKAIKE M, et al.ERK5 activation in macrophages promotes efferocytosis and inhibits atherosclerosis[J].Circulation,2014,130(2):180-191. |
| [10] | CHE Z B, CAO X T.Flow cytometry: principle of operation and application[M].2nd ed. Beijing:Science Press,2014:166-167. |
| [11] | HOCHREITER-HUFFORD A, RAVICHANDRAN K S.Clearing the dead:apoptotic cell sensing, recognition,engulfment,and digestion[J].Cold Spring Harb Perspect Biol,2013,5(1):a008748. |
| [12] | ELLIOTT M R, RAVICHANDRAN K S.The dynamics of apoptotic cell clearance[J].Dev cell,2016,38(2):147-160. |
| [13] | VAN DER MEER J H, VAN DER POLL T, VAN'T VEER C. TAM receptors, Gas6, and protein S: roles in inflammation and hemostasis[J].Blood,2014,123(16):2460-2469. |
| [14] | NAKAYA M, TAJIMA M, KOSAKO H, et al.GRK6 deficiency in mice causes autoimmune disease due to impaired apoptotic cell clearance[J].Nat Commun,2013,4(2):1532. |
| [15] | TSOU W I, NAUYEN K Q, CALARESE D A, et al.Receptor tyrosine kinases, TYRO3, AXL, and MER, demonstrate distinct patterns and complexregulation of ligand-induced activation[J].J Biol Chem,2014,289(37):25750-25763. |
| [16] | SARODE G S, SARODE S C, MANIYAR N, et al.Carcinogenesis-relevant biological events in the pathophysiology of the efferocytosis phenomenon[J].Oncol Rev,2017,11(2):343. |
| [17] | LINGER R M, KEATING A K, EARP H S, et al.TAM receptor tyrosine kinases:Biologic functions, signaling, and potential therapeutic targeting in human cancer[J].Adv Cancer Res,2008,100:35-83. |
| [18] | VERMA A, WARNER S L, VANKAYALAPATI H, et al.Targeting Axl and Mer kinases in cancer[J]. Mol Cancer Ther,2011,10(10):1763-1773. |
| [19] | HOANG V T, YAN T J, CAVANAUGH J E, et al.Oncogenic signaling of MEK5-ERK5[J].Cancer Lett,2017,392:51-59. |
| [20] | 王建茹, 刘萍. 胞外信号调节激酶5与动脉粥样硬化关系的研究进展[J].中华中医药学刊,2016,34(9): 2126-2129. |
| [21] | WANG J R, LIU P.Advances in the research of relationship between ERK5 and atherosclerosis[J].Chinese Archives of Traditional Chinese Medicine,2016,34(9): 2126-2129. |
