High Glucose Induces the Aging of Mesenchymal Stem Cells Via Akt/mTOR Signaling

Overview

Journal Mol Med Rep

Specialty Molecular Biology

Date 2017 Jun 29

PMID 28656269

Citations 34

Authors

Dayong Zhang

Huifei Lu

Zhongxing Chen

Yayan Wang

Jiuzhou Lin

Shan Xu

Chong Zhang

Baoming Wang

Zhanggen Yuan

Xiao Feng

Xuefan Jiang

Jianping Pan

Affiliations

Soon will be listed here.

Abstract

It has previously been demonstrated that glucose is important in the process of stem cell aging. However, the mechanisms of cell senescence induced by high glucose (HG) remain to be elucidated. The preliminary study indicated that D‑galactose induced mesenchymal stem cell (MSCs) aging. The present study demonstrated, following treatment with 11.0 or 22.0 mM HG for 14 days, that HG significantly promoted MSCs aging and the expression levels of phosphorylated (p-)phosphatidylinositol 3-kinase/protein kinase B (Akt) and p‑mammalian target of rapamycin signaling (mTOR) in the HG groups were increased compared with the control group. However, following Akt inhibition with 1.0 or 10.0 nM MK‑2206, which is an Akt‑specific small molecule inhibitor, the senescence‑cell value in the HG group was significantly decreased compared with the control group. These results indicated that HG induced MSCs senescence and this effect was primarily mediated via the Akt/mTOR signaling pathway.

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References

Mehrfarjam Z, Esmaeili F, Shabani L, Ebrahimie E . Induction of pancreatic β cell gene expression in mesenchymal stem cells. Cell Biol Int. 2015; 40(5):486-500. DOI: 10.1002/cbin.10567. View

Schultz M, Sinclair D . When stem cells grow old: phenotypes and mechanisms of stem cell aging. Development. 2016; 143(1):3-14. PMC: 4725211. DOI: 10.1242/dev.130633. View

Rekittke N, Ang M, Rawat D, Khatri R, Linn T . Regenerative Therapy of Type 1 Diabetes Mellitus: From Pancreatic Islet Transplantation to Mesenchymal Stem Cells. Stem Cells Int. 2016; 2016():3764681. PMC: 4800095. DOI: 10.1155/2016/3764681. View

Koci Z, Turnovcova K, Dubsky M, Baranovicova L, Holan V, Chudickova M . Characterization of human adipose tissue-derived stromal cells isolated from diabetic patient's distal limbs with critical ischemia. Cell Biochem Funct. 2014; 32(7):597-604. DOI: 10.1002/cbf.3056. View

Alt E, Senst C, Murthy S, Slakey D, Dupin C, Chaffin A . Aging alters tissue resident mesenchymal stem cell properties. Stem Cell Res. 2012; 8(2):215-25. DOI: 10.1016/j.scr.2011.11.002. View

Ferraro F, Lymperi S, Mendez-Ferrer S, Saez B, Spencer J, Yeap B . Diabetes impairs hematopoietic stem cell mobilization by altering niche function. Sci Transl Med. 2011; 3(104):104ra101. PMC: 3754876. DOI: 10.1126/scitranslmed.3002191. View

Liu L, Hu X, Cai G, Lv Y, Zhuo L, Gao J . High glucose-induced hypertrophy of mesangial cells is reversed by connexin43 overexpression via PTEN/Akt/mTOR signaling. Nephrol Dial Transplant. 2011; 27(1):90-100. DOI: 10.1093/ndt/gfr265. View

Raggi C, Berardi A . Mesenchymal stem cells, aging and regenerative medicine. Muscles Ligaments Tendons J. 2013; 2(3):239-42. PMC: 3666525. View

Nogal M, Troyano N, Calleros L, Griera M, Rodriguez-Puyol M, Rodriguez-Puyol D . Hyperosmolarity induced by high glucose promotes senescence in human glomerular mesangial cells. Int J Biochem Cell Biol. 2014; 54:98-110. DOI: 10.1016/j.biocel.2014.07.006. View

10.

Khan M, Mohsin S, Khan S, Riazuddin S . Repair of senescent myocardium by mesenchymal stem cells is dependent on the age of donor mice. J Cell Mol Med. 2010; 15(7):1515-27. PMC: 3823196. DOI: 10.1111/j.1582-4934.2009.00998.x. View

11.

Wakao S, Kuroda Y, Ogura F, Shigemoto T, Dezawa M . Regenerative Effects of Mesenchymal Stem Cells: Contribution of Muse Cells, a Novel Pluripotent Stem Cell Type that Resides in Mesenchymal Cells. Cells. 2014; 1(4):1045-60. PMC: 3901150. DOI: 10.3390/cells1041045. View

12.

Estrada J, Torres Y, Benguria A, Dopazo A, Roche E, Carrera-Quintanar L . Human mesenchymal stem cell-replicative senescence and oxidative stress are closely linked to aneuploidy. Cell Death Dis. 2013; 4:e691. PMC: 3702285. DOI: 10.1038/cddis.2013.211. View

13.

Chang T, Hsu M, Wu K . High glucose induces bone marrow-derived mesenchymal stem cell senescence by upregulating autophagy. PLoS One. 2015; 10(5):e0126537. PMC: 4427318. DOI: 10.1371/journal.pone.0126537. View

14.

De Miguel M, Fuentes-Julian S, Blazquez-Martinez A, Pascual C, Aller M, Arias J . Immunosuppressive properties of mesenchymal stem cells: advances and applications. Curr Mol Med. 2012; 12(5):574-91. DOI: 10.2174/156652412800619950. View

15.

Montes D, Brenet M, Munoz V, Burgos P, Villanueva C, Figueroa C . Vasopressin activates Akt/mTOR pathway in smooth muscle cells cultured in high glucose concentration. Biochem Biophys Res Commun. 2013; 441(4):923-8. DOI: 10.1016/j.bbrc.2013.10.169. View

16.

Zhang D, Pan Y, Zhang C, Yan B, Yu S, Wu D . Wnt/β-catenin signaling induces the aging of mesenchymal stem cells through promoting the ROS production. Mol Cell Biochem. 2012; 374(1-2):13-20. DOI: 10.1007/s11010-012-1498-1. View

17.

Asumda F . Age-associated changes in the ecological niche: implications for mesenchymal stem cell aging. Stem Cell Res Ther. 2013; 4(3):47. PMC: 3706986. DOI: 10.1186/scrt197. View

18.

Hashemian S, Kouhnavard M, Nasli-Esfahani E . Mesenchymal Stem Cells: Rising Concerns over Their Application in Treatment of Type One Diabetes Mellitus. J Diabetes Res. 2015; 2015:675103. PMC: 4630398. DOI: 10.1155/2015/675103. View

19.

Sun Y, Chen L, Hou X, Hou W, Dong J, Sun L . Differentiation of bone marrow-derived mesenchymal stem cells from diabetic patients into insulin-producing cells in vitro. Chin Med J (Engl). 2007; 120(9):771-6. View

20.

Miura Y . Guest editorial: Human mesenchymal stromal/stem cell (MSC). Int J Hematol. 2015; 103(2):119-21. DOI: 10.1007/s12185-015-1931-9. View