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

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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.	鄭鈞豐, 陳潔, 顧艷艷, 等. 紅景天苷的研究進展. 西南國防醫藥, 2013, 23(12): 1386-1388.
2.	張曉東. 紅景天苷的研究進展. 中外健康文摘, 2014(27): 158-159.
3.	趙玲, 趙紅斌, 潘茜, 等. 紅景天苷誘導骨髓間充質干細胞向神經元樣細胞分化中的 Ca²⁺/CaM 信號通路. 中國組織工程研究, 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.	馮利杰, 王海萍, 沈玉先. 內質網應激與神經元退行性變. 中國藥理學通報, 2007, 23(4): 428-432.
8.	尚偉, 遲兆富. 熱休克蛋白與神經系統. 國外醫學: 生理, 病理科學與臨床分冊, 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.	張霞, 曹榮峰, 叢霞, 等. CaM 對小鼠胎兒成纖維細胞 Hsp70 表達的影響. 中國農業科學, 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, 謝秀杰, 魏群. Ⅰ 型蛋白磷酸酶研究進展. 微生物學報, 2008, 48(2): 269-273.
19.	廖儒佳, 曹雯雯, 張偉. 蛋白磷酸酶 1 與 Ca²⁺/鈣調素依賴性蛋白激酶 Ⅱ 在心肌病中研究進展. 中國藥理學通報, 2012, 28(12): 1629-1633.
20.	胡躍強, 唐農, 董少龍, 等. 清熱化瘀方對腦缺血預處理大鼠 GADD34 表達的影響. 中藥新藥與臨床藥理, 2012, 23(1): 48-51.
21.	張海菊, 姚寶珍, 凌偉. COX-2 抑制劑對幼鼠反復癇性發作后神經發生的影響. 癲癇與神經電生理學雜志, 2011, 20(4): 196-206.
22.	陳左然, 張祥建. 環氧合酶-2 與中樞神經系統疾病. 國外醫學: 腦血管疾病分冊, 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.	陳亞男. 紅景天苷通過 ERK1/2 和 PI_3K/AKT/mTOR 信號通路介導小鼠骨髓間充質干細胞向神經元樣細胞定向分化的研究. 蘭州: 蘭州大學, 2014.
27.	張藍, 孫中偉, 黃剛, 等. 突變型人胰高血糖素樣肽-1 對神經細胞損傷的保護. 中國現代應用藥學, 2012(03): 185-191.
28.	許佳, 許小青, 曹雪濤. IL-2 受體信號轉導及其功能研究進展. 中國免疫學雜志, 2014, 30(3): 416-422.
29.	王建明. IL-2-神經及免疫系統的調節因子. 海南醫學, 2006, 17(9): 154-155.
30.	呂志敢, 郭政. 腫瘤壞死因子的研究進展. 山西醫科大學學報, 2006, 37(3): 311-314.
31.	婁遠蕾, 鄧志鋒, 賴賢良, 等. TNF-α 體外誘導 rMSC 向神經細胞分化的研究. 實驗與檢驗醫學, 2010, 28(1): 25-26.
32.	武小路. 生長抑素的分布及其功能研究進展. 運動, 2012(12): 143-145.

1. 鄭鈞豐, 陳潔, 顧艷艷, 等. 紅景天苷的研究進展. 西南國防醫藥, 2013, 23(12): 1386-1388.
2. 張曉東. 紅景天苷的研究進展. 中外健康文摘, 2014(27): 158-159.
3. 趙玲, 趙紅斌, 潘茜, 等. 紅景天苷誘導骨髓間充質干細胞向神經元樣細胞分化中的 Ca²⁺/CaM 信號通路. 中國組織工程研究, 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. 馮利杰, 王海萍, 沈玉先. 內質網應激與神經元退行性變. 中國藥理學通報, 2007, 23(4): 428-432.
8. 尚偉, 遲兆富. 熱休克蛋白與神經系統. 國外醫學: 生理, 病理科學與臨床分冊, 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. 張霞, 曹榮峰, 叢霞, 等. CaM 對小鼠胎兒成纖維細胞 Hsp70 表達的影響. 中國農業科學, 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, 謝秀杰, 魏群. Ⅰ 型蛋白磷酸酶研究進展. 微生物學報, 2008, 48(2): 269-273.
19. 廖儒佳, 曹雯雯, 張偉. 蛋白磷酸酶 1 與 Ca²⁺/鈣調素依賴性蛋白激酶 Ⅱ 在心肌病中研究進展. 中國藥理學通報, 2012, 28(12): 1629-1633.
20. 胡躍強, 唐農, 董少龍, 等. 清熱化瘀方對腦缺血預處理大鼠 GADD34 表達的影響. 中藥新藥與臨床藥理, 2012, 23(1): 48-51.
21. 張海菊, 姚寶珍, 凌偉. COX-2 抑制劑對幼鼠反復癇性發作后神經發生的影響. 癲癇與神經電生理學雜志, 2011, 20(4): 196-206.
22. 陳左然, 張祥建. 環氧合酶-2 與中樞神經系統疾病. 國外醫學: 腦血管疾病分冊, 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. 陳亞男. 紅景天苷通過 ERK1/2 和 PI_3K/AKT/mTOR 信號通路介導小鼠骨髓間充質干細胞向神經元樣細胞定向分化的研究. 蘭州: 蘭州大學, 2014.
27. 張藍, 孫中偉, 黃剛, 等. 突變型人胰高血糖素樣肽-1 對神經細胞損傷的保護. 中國現代應用藥學, 2012(03): 185-191.
28. 許佳, 許小青, 曹雪濤. IL-2 受體信號轉導及其功能研究進展. 中國免疫學雜志, 2014, 30(3): 416-422.
29. 王建明. IL-2-神經及免疫系統的調節因子. 海南醫學, 2006, 17(9): 154-155.
30. 呂志敢, 郭政. 腫瘤壞死因子的研究進展. 山西醫科大學學報, 2006, 37(3): 311-314.
31. 婁遠蕾, 鄧志鋒, 賴賢良, 等. TNF-α 體外誘導 rMSC 向神經細胞分化的研究. 實驗與檢驗醫學, 2010, 28(1): 25-26.
32. 武小路. 生長抑素的分布及其功能研究進展. 運動, 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