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The Influence of High D-glucose Concentrations on Increasing the Expression of EGR-1, PTEN and GGPS-1 Involved in Insulin Resistance of AT-MSCs

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8th International Conference on the Development of Biomedical Engineering in Vietnam (BME 2020)

Part of the book series: IFMBE Proceedings ((IFMBE,volume 85))

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Abstract

Type 2 diabetes mellitus (T2DM) is increasing worldwide, characterized by insulin resistance and hyperglycemia. The results of previous studies have demonstrated that high D-glucose concentrations alter the characteristic and function of adipose tissue-derived mesenchymal stem cells (AT-MSCs). Besides, early growth response factor-1 (EGR-1) and insulin resistance mediators (PTEN and GGPS-1) were highly upregulated in diabetic AT-MSCs (dAT-MSCs) compared with non-diabetic AT-MSCs (nAT-MSCs). In this research, we examined the effect of high glucose concentrations on nAT-MSCs in comparison to dAT-MSCs on the expression of EGR-1, PTEN, and GGPS-1 involved in insulin resistance of human AT-MSCs. The expression of insulin resistance-related genes and EGR-1 protein were analyzed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot, respectively. The results show that the high D-Glucose concentrations (25, 50, and 100 mM) enhanced the expression of EGR-1 and insulin resistance-related genes in nAT-MSCs compared with non-treated nAT-MSCs and dAT-MSCs. Notably, the increase of high D-Glucose concentration remarkably upregulated the expression of EGR-1, PTEN, and GGPS-1 in both nAT-MSCs and dAT-MSCs. The effect of high D-glucose concentration (100 mM) remarkably increased the expression of EGR-1, PTEN, and GGPS-1 in human AT-MSCs. The results of this study will expand our knowledge about the impact of high glucose concentration on insulin resistance in human AT-MSCs for the improvement in diabetic treatment.

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Abbreviations

EGR-1 :

Early growth response-1

PTEN :

Phosphatase and tensin homologue

GGPS-1 :

Geranylgeranyl diphosphate synthase-1

IRS-1 :

Insulin receptor substrate-1

References

  1. Cramer EFC, Jones RK, Slakey DP, Dupin CL, Newsome ER, Alt EU, Izadpanah R (2010) Persistent high glucose concentrations alter the regenerative potential of mesenchymal stem cells. Stem Cells Dev 19:1875–1884. https://doi.org/10.1089/scd.2010.0009

    Article  Google Scholar 

  2. Groop L, DeFronzo RA, Ferrannini E, Henry RR, Herman WH, Holst JJ, Hu FB, Kahn CR, Raz I, Shulman GI, Simonson DC (2015). Type 2 diabetes mellitus. Nat Rev. https://doi.org/10.1038/nrdp.2015.19

  3. Xiao S, Pillay TS, Olefsky JM (1996) Glucose-induced phosphorylation of the insulin receptor—functional effects and characterization of phosphorylation sites. Am Soc Clinx Invest 97:613–620. https://doi.org/10.1172/JCI118457

    Article  Google Scholar 

  4. Renström JBF, Svensson M, Eriksson JW (2007) Insulin resistance induced by high glucose and high insulin precedes insulin receptor substrate 1 protein depletion in human adipocytes. Metab Clin Exp 56:190–198. https://doi.org/10.1016/j.metabol.2006.09.012

    Article  Google Scholar 

  5. Ning XY, Shen F-Y, Gao X, Xue B, Li C-J (2011) An early response transcription factor, Egr-1, enhances insulin resistance in type 2 diabetes with chronic hyperinsulinism. J Biol Chem 286:14508–14515. https://doi.org/10.1074/jbc.M110.190165

    Article  Google Scholar 

  6. Ning Shen Xiao Yu, Zhang M-L, Pan F-Y, Wang C, Jia W-P, Liu C, Gao Q, Gao X, Xue B, Li C-J (2011) Egr-1 decreases adipocyte insulin sensitivity by tilting PI3K/Akt and MAPK signal balance in mice. EMBO J 30:3754–3765. https://doi.org/10.1038/emboj.2011.277

    Article  Google Scholar 

  7. Trinh T-T, Ohneda K, Kimura K, Salazar GT, Sato F, Ohneda O (2016) Increased expression of EGR-1 in diabetic human adipose tissue-derived mesenchymal stem cells reduces their wound healing capacity. Stem Cells Dev 25:760–773. https://doi.org/10.1089/scd.2015.0335

    Article  Google Scholar 

  8. Kern HES, Stoeve J, Klüter H, Bieback K (2006) Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 24:1294–1301. https://doi.org/10.1634/stemcells.2005-0342

    Article  Google Scholar 

  9. Benisch P, Schilling T, Li YM, Zeck S, Meissner-Weigl J, Schneider D, Limbert C, Seufert J, Kassem M, Schütze N, Jakob F (2007) Effects of high glucose on mesenchymal stem cell proliferation and differentiation. Biochem Biophys Res Commun 363:209–215. https://doi.org/10.1016/j.bbrc.2007.08.161

  10. Kimura MNK, Salazar G, Yamashita T, Tsuboi I, Mishima H, Matsushita S, Sato F, Yamagata K, Ohneda O (2014) The role of CCL5 in the ability of adipose tissue-derived mesenchymal stem cells to support repair of ischemic regions. Stem Cells Dev 23:488–501. https://doi.org/10.1089/scd.2013.0307

    Article  Google Scholar 

  11. Seeberger KL, Yeung TY, Kin T, Adesida A, Jomha N, James Shapiro AM, Korbutt GS (2012) Human mesenchymal stem cells protect human islets from pro-inflammatory cytokines. PLoS One 7. https://doi.org/10.1371/journal.pone.0038189

  12. Trinh TYNT, Tran Cam Tu, Kato T, Ohneda K, Sato F, Ohneda O (2016) Microvesicles enhance the mobility of human diabetic adipose tissuederived mesenchymal stem cells in vitro and improve wound healing in vivo. Biochem Biophys Res Commun 473:1111–1118. https://doi.org/10.1016/j.bbrc.2016.04.025

    Article  Google Scholar 

  13. Aguiari BZSLP, Vindigni V, Rimessi A, Bianchi K, Franzin C, Cortivo R, Rossato M, Vettor R, Abatangelo G, Pozzan T, Pinton P, Rizzuto R (2008) High glucose induces adipogenic differentiation of muscle-derived stem cells. PNAS 105:1226–1231. https://doi.org/10.1073/pnas.0711402105

    Article  Google Scholar 

  14. Jianming HH, Guo JG, Bai H, He H, Assi R, Isaji T, Wang T, Setia O, Lopes L, Yongquan Gu, Dardik A (2018) Adipose-derived mesenchymal stem cells accelerate diabetic wound healing in a similar fashion as bone marrow-derived cells. Am J Physiol Cell Physiol 315:885–896. https://doi.org/10.1152/ajpcell.00120.2018

    Article  Google Scholar 

  15. Rosivatz E (2007) Inhibiting PTEN. Biochem Soc Trans 35:257–259. https://doi.org/10.1042/BST0350257

    Article  Google Scholar 

  16. Dey CS, Gupta A (2012) PTEN, a widely known negative regulator of insulin/PI3K signaling, positively regulates neuronal insulin resistance. Mol Biol Cell 23:3882–3898. https://doi.org/10.1091/mbc.E12-05-0337

  17. SørensenLR, Josefsen K, Buschard K, Birkenbach M (1999) Glucose induces early growth response gene (Egr-1) expression in pancreatic beta cells. Diabetologia 42:195–203. https://doi.org/10.1007/s001250051139

  18. Castoldi M, Horn P, Wagner W, Diehlmann A, Bork S, Saffrich R, Benes V, Blake J, Pfister S, Eckstein V, Ho AD (2008) Replicative senescence of mesenchymal stem cells: a continuous and organized process. PLoS ONE 3. https://doi.org/10.1371/journal.pone.0002213

  19. Munsey TS, Abuarab N, Jiang L-H,Li J, Sivaprasadarao A (2017) High glucose-induced ROS activates TRPM2 to trigger lysosomal membrane permeabilization and Zn2+-mediated mitochondrial fission. Sci Signal 10. https://doi.org/10.1126/scisignal.aal4161

  20. Song G, Cao X, Shao X, Zhao Y, Shi B (2014) Metformin rescues the MG63 osteoblasts against the effect of high glucose on proliferation. J Diabetes Res 2014. https://doi.org/10.1155/2014/453940

  21. Rukhsana SP, Hasan N, Harada S (2003) Differential regulation of early growth response gene-1 expression by insulin and glucose in vascular endothelial cells, arteriosclerosis. Thromb Vasc Biol 23:988–993. https://doi.org/10.1161/01.ATV.0000071351.07784.19

    Article  Google Scholar 

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Acknowledgements

The authors thank to the financial support by the grant from the Biotechnology Center of Ho Chi Minh City (DV01/17-19). We also thank professor Osamu Ohneda for providing stem cells.

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The authors declare no conflict of interest.

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Correspondence to Nhu-Thuy Trinh .

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Mai, HP., Trinh, NT., Long, V.B., Binh, N.T., Nguyen, DQ., Duong, HX. (2022). The Influence of High D-glucose Concentrations on Increasing the Expression of EGR-1, PTEN and GGPS-1 Involved in Insulin Resistance of AT-MSCs. In: Van Toi, V., Nguyen, TH., Long, V.B., Huong, H.T.T. (eds) 8th International Conference on the Development of Biomedical Engineering in Vietnam. BME 2020. IFMBE Proceedings, vol 85. Springer, Cham. https://doi.org/10.1007/978-3-030-75506-5_42

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  • DOI: https://doi.org/10.1007/978-3-030-75506-5_42

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