Role and mechanism of cAMP/Ca<sup>2+</sup> signal pathway in differentiation of bone marrow mesenchymal stem cells into neuronal cells induced by salidroside _Journal of Biomedical Engineering

Authors：

ZHAO Ling ¹ ,  ZHAO Hongbin ² , QIN Wen ² , LI Gen ² , TANG Junjie ² , WANG Jiuna ²

1. Department of Pathology, Lanzhou University Second Hospital, Lanzhou 730000, P.R.China;
2. Institute of Orthopaedics, Lanzhou General Hospital of PLA, Lanzhou 730000, P.R.China;

Corresponding author：

ZHAO Hongbin, Email: zhao761032@163.com

Keywords：

salidroside; bone marrow mesenchymal stem cells; neuronal cells; AMP/Ca²⁺ signaling pathway; expression profiles of RNA

DOI：

10.7507/1001-5515.201505037

Video：

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To investigate the mechanism of cAMP/Ca²⁺ signaling pathway inducing bone marrow mesenchymal stem cells to differentiate into neuronal cells, we cultured the bone marrow mesenchymal stem cells D1 cells in the present study. D1 cells were divided into two groups: control group and salidroside inducing groups. Control group was cultured with complete culture solution D/F12, while salidroside inducing groups were induced with 100 mg·L^–1 salidroside for different time periods (24, 48 and 72 hours). PCR-array assay was used to detect expression of 84 calcium related mRNA, and significantly different genes were chosen to analyse. As a result, there were 4 significantly upregulated mRNAs inclu-ding DNA damage-inducible transcript 3 (Ddit3), heat shock protein 5 (Hspa5), protein phosphatase 1 regulatory subunit (Ppp1r15a) and prostaglandin-endoperoxide synthase 2 (Ptgs-2), and 4 significantly downregulated mRNAs including glucagon (Gcg), interleukin 2 (Il2), tumor necrosis factor (Tnf) and somatostatin (Sst) in the cAMP/Ca²⁺ signaling pathway. They probably had an effect on the process of salidroside induced D1 cells differentiating into neuronal cells.

Citation： ZHAO Ling, ZHAO Hongbin, QIN Wen, LI Gen, TANG Junjie, WANG Jiuna. Role and mechanism of cAMP/Ca²⁺ signal pathway in differentiation of bone marrow mesenchymal stem cells into neuronal cells induced by salidroside . Journal of Biomedical Engineering, 2017, 34(3): 401-408. doi: 10.7507/1001-5515.201505037 Copy

1.	郑钧丰, 陈洁, 顾艳艳, 等. 红景天苷的研究进展. 西南国防医药, 2013, 23(12): 1386-1388.
2.	张晓东. 红景天苷的研究进展. 中外健康文摘, 2014(27): 158-159.
3.	赵玲, 赵红斌, 潘茜, 等. 红景天苷诱导骨髓间充质干细胞向神经元样细胞分化中的 Ca²⁺/CaM 信号通路. 中国组织工程研究, 2014(37): 6019-6023.
4.	Novoa I, Zeng H, Harding H P, et al. Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2α. J Cell Biol, 2001, 153(5): 1011-1022.
5.	Galehdar Z, Swan P, Fuerth B, et al. Neuronal apoptosis induced by endoplasmic reticulum stress is regulated by ATF4-CHOP-mediated induction of the Bcl-2 homology 3-only member PUMA. J Neurosci, 2010, 30(50): 16938-16948.
6.	Li Gang, Mongillo M, Chin K T, et al. Role of ERO1-α-mediated stimulation of inositol 1, 4, 5-triphosphate receptor activity in endoplasmic reticulum stress-induced apoptosis. J Cell Biol, 2009, 186(6): 783-792.
7.	冯利杰, 王海萍, 沈玉先. 内质网应激与神经元退行性变. 中国药理学通报, 2007, 23(4): 428-432.
8.	尚伟, 迟兆富. 热休克蛋白与神经系统. 国外医学: 生理, 病理科学与临床分册, 1999(06): 337-340.
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12.	张霞, 曹荣峰, 丛霞, 等. CaM 对小鼠胎儿成纤维细胞 Hsp70 表达的影响. 中国农业科学, 2011, 44(7): 1495-1501.
13.	Holmberg C I, Hietakangas V, Mikhailov A, et al. Phosphorylation of serine 230 promotes inducible transcriptional activity of heat shock factor 1. EMBO J, 2001, 20(14): 3800-3810.
14.	Voellmy R. Feedback regulation of the heat shock response// Starke B K, Gaestel M. Molecular Chaperones in Health and Disease. Berlin Heidelberg: Springer Berlin Heidelberg, 2006: 43-68.
15.	Yano S, Morioka M, Kuratsu J I, et al. Functional proteins involved in regulation of intracellular Ca²⁺ for drug development: role of calcium/calmodulin-dependent protein kinases in ischemic neuronal death. J Pharmacol Sci, 2005, 97(3): 351-354.
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17.	Tsui J, Inagaki M, Schulman H. Calcium/Calmodulin-dependent protein kinase II (CaMKII) localization acts in concert with substrate targeting to create spatial restriction for phosphorylation[J]. J Biol Chem, 2005, 280(10): 9210-9216.
18.	王柏婧, 谢秀杰, 魏群. Ⅰ 型蛋白磷酸酶研究进展. 微生物学报, 2008, 48(2): 269-273.
19.	廖儒佳, 曹雯雯, 张伟. 蛋白磷酸酶 1 与 Ca²⁺/钙调素依赖性蛋白激酶 Ⅱ 在心肌病中研究进展. 中国药理学通报, 2012, 28(12): 1629-1633.
20.	胡跃强, 唐农, 董少龙, 等. 清热化瘀方对脑缺血预处理大鼠 GADD34 表达的影响. 中药新药与临床药理, 2012, 23(1): 48-51.
21.	张海菊, 姚宝珍, 凌伟. COX-2 抑制剂对幼鼠反复痫性发作后神经发生的影响. 癫痫与神经电生理学杂志, 2011, 20(4): 196-206.
22.	陈左然, 张祥建. 环氧合酶-2 与中枢神经系统疾病. 国外医学: 脑血管疾病分册, 2005, 13(3): 228-231.
23.	Meffert M K, Chang J M, Wiltgen B J, et al. NF-κB functions in synaptic signaling and behavior. Nat Neurosci, 2003, 6(10): 1072-1078.
24.	Choudhary S, Kumar A, Kale R K, et al. Extracellular calcium induces COX-2 in osteoblasts via a PKA pathway. Biochem Biophys Res Commun, 2004, 322(2): 395-402.
25.	Ogata S, Kubota Y, Satoh S, et al. Ca²⁺ stimulates COX-2 expression through calcium-sensing receptor in fibroblasts. Biochem Biophys Res Commun, 2006, 351(4): 808-814.
26.	陈亚男. 红景天苷通过 ERK1/2 和 PI_3K/AKT/mTOR 信号通路介导小鼠骨髓间充质干细胞向神经元样细胞定向分化的研究. 兰州: 兰州大学, 2014.
27.	张蓝, 孙中伟, 黄刚, 等. 突变型人胰高血糖素样肽-1 对神经细胞损伤的保护. 中国现代应用药学, 2012(03): 185-191.
28.	许佳, 许小青, 曹雪涛. IL-2 受体信号转导及其功能研究进展. 中国免疫学杂志, 2014, 30(3): 416-422.
29.	王建明. IL-2-神经及免疫系统的调节因子. 海南医学, 2006, 17(9): 154-155.
30.	吕志敢, 郭政. 肿瘤坏死因子的研究进展. 山西医科大学学报, 2006, 37(3): 311-314.
31.	娄远蕾, 邓志锋, 赖贤良, 等. TNF-α 体外诱导 rMSC 向神经细胞分化的研究. 实验与检验医学, 2010, 28(1): 25-26.
32.	武小路. 生长抑素的分布及其功能研究进展. 运动, 2012(12): 143-145.

1. 郑钧丰, 陈洁, 顾艳艳, 等. 红景天苷的研究进展. 西南国防医药, 2013, 23(12): 1386-1388.
2. 张晓东. 红景天苷的研究进展. 中外健康文摘, 2014(27): 158-159.
3. 赵玲, 赵红斌, 潘茜, 等. 红景天苷诱导骨髓间充质干细胞向神经元样细胞分化中的 Ca²⁺/CaM 信号通路. 中国组织工程研究, 2014(37): 6019-6023.
4. Novoa I, Zeng H, Harding H P, et al. Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2α. J Cell Biol, 2001, 153(5): 1011-1022.
5. Galehdar Z, Swan P, Fuerth B, et al. Neuronal apoptosis induced by endoplasmic reticulum stress is regulated by ATF4-CHOP-mediated induction of the Bcl-2 homology 3-only member PUMA. J Neurosci, 2010, 30(50): 16938-16948.
6. Li Gang, Mongillo M, Chin K T, et al. Role of ERO1-α-mediated stimulation of inositol 1, 4, 5-triphosphate receptor activity in endoplasmic reticulum stress-induced apoptosis. J Cell Biol, 2009, 186(6): 783-792.
7. 冯利杰, 王海萍, 沈玉先. 内质网应激与神经元退行性变. 中国药理学通报, 2007, 23(4): 428-432.
8. 尚伟, 迟兆富. 热休克蛋白与神经系统. 国外医学: 生理, 病理科学与临床分册, 1999(06): 337-340.
9. Ortiz C, Cardemil L. Heat-shock responses in two leguminous plants: a comparative study. J Exp Bot, 2001, 52(361): 1711-1719.
10. Welch W J. Mammalian stress response: cell physiology, structure/function of stress proteins, and implications for medicine and disease. Physiol Rev, 1992, 72(4): 1063-1081.
11. Mariano T M, Siekierka J. Inhibition of HeLa cell protein synthesis under heat shock conditions in the absence of initiation factor eIF-2α phosphorylation. Biochem Biophys Res Commun, 1986, 138(2): 519-525.
12. 张霞, 曹荣峰, 丛霞, 等. CaM 对小鼠胎儿成纤维细胞 Hsp70 表达的影响. 中国农业科学, 2011, 44(7): 1495-1501.
13. Holmberg C I, Hietakangas V, Mikhailov A, et al. Phosphorylation of serine 230 promotes inducible transcriptional activity of heat shock factor 1. EMBO J, 2001, 20(14): 3800-3810.
14. Voellmy R. Feedback regulation of the heat shock response// Starke B K, Gaestel M. Molecular Chaperones in Health and Disease. Berlin Heidelberg: Springer Berlin Heidelberg, 2006: 43-68.
15. Yano S, Morioka M, Kuratsu J I, et al. Functional proteins involved in regulation of intracellular Ca²⁺ for drug development: role of calcium/calmodulin-dependent protein kinases in ischemic neuronal death. J Pharmacol Sci, 2005, 97(3): 351-354.
16. Kang D, Hur C G, Park J Y, et al. Acetylcholine increases Ca²⁺ influx by activation of CaMKII in mouse oocytes. Biochem Biophys Res Commun, 2007, 360(2): 476-482.
17. Tsui J, Inagaki M, Schulman H. Calcium/Calmodulin-dependent protein kinase II (CaMKII) localization acts in concert with substrate targeting to create spatial restriction for phosphorylation[J]. J Biol Chem, 2005, 280(10): 9210-9216.
18. 王柏婧, 谢秀杰, 魏群. Ⅰ 型蛋白磷酸酶研究进展. 微生物学报, 2008, 48(2): 269-273.
19. 廖儒佳, 曹雯雯, 张伟. 蛋白磷酸酶 1 与 Ca²⁺/钙调素依赖性蛋白激酶 Ⅱ 在心肌病中研究进展. 中国药理学通报, 2012, 28(12): 1629-1633.
20. 胡跃强, 唐农, 董少龙, 等. 清热化瘀方对脑缺血预处理大鼠 GADD34 表达的影响. 中药新药与临床药理, 2012, 23(1): 48-51.
21. 张海菊, 姚宝珍, 凌伟. COX-2 抑制剂对幼鼠反复痫性发作后神经发生的影响. 癫痫与神经电生理学杂志, 2011, 20(4): 196-206.
22. 陈左然, 张祥建. 环氧合酶-2 与中枢神经系统疾病. 国外医学: 脑血管疾病分册, 2005, 13(3): 228-231.
23. Meffert M K, Chang J M, Wiltgen B J, et al. NF-κB functions in synaptic signaling and behavior. Nat Neurosci, 2003, 6(10): 1072-1078.
24. Choudhary S, Kumar A, Kale R K, et al. Extracellular calcium induces COX-2 in osteoblasts via a PKA pathway. Biochem Biophys Res Commun, 2004, 322(2): 395-402.
25. Ogata S, Kubota Y, Satoh S, et al. Ca²⁺ stimulates COX-2 expression through calcium-sensing receptor in fibroblasts. Biochem Biophys Res Commun, 2006, 351(4): 808-814.
26. 陈亚男. 红景天苷通过 ERK1/2 和 PI_3K/AKT/mTOR 信号通路介导小鼠骨髓间充质干细胞向神经元样细胞定向分化的研究. 兰州: 兰州大学, 2014.
27. 张蓝, 孙中伟, 黄刚, 等. 突变型人胰高血糖素样肽-1 对神经细胞损伤的保护. 中国现代应用药学, 2012(03): 185-191.
28. 许佳, 许小青, 曹雪涛. IL-2 受体信号转导及其功能研究进展. 中国免疫学杂志, 2014, 30(3): 416-422.
29. 王建明. IL-2-神经及免疫系统的调节因子. 海南医学, 2006, 17(9): 154-155.
30. 吕志敢, 郭政. 肿瘤坏死因子的研究进展. 山西医科大学学报, 2006, 37(3): 311-314.
31. 娄远蕾, 邓志锋, 赖贤良, 等. TNF-α 体外诱导 rMSC 向神经细胞分化的研究. 实验与检验医学, 2010, 28(1): 25-26.
32. 武小路. 生长抑素的分布及其功能研究进展. 运动, 2012(12): 143-145.

Journal of Biomedical Engineering

Role and mechanism of cAMP/Ca²⁺ signal pathway in differentiation of bone marrow mesenchymal stem cells into neuronal cells induced by salidroside

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Journal of Biomedical Engineering

Role and mechanism of cAMP/Ca2+ signal pathway in differentiation of bone marrow mesenchymal stem cells into neuronal cells induced by salidroside

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Role and mechanism of cAMP/Ca²⁺ signal pathway in differentiation of bone marrow mesenchymal stem cells into neuronal cells induced by salidroside