Inhibition of autophagy alleviates the senescent state of rat mesenchymal stem cells during long-term culture

  • Authors:
    • Yong Zheng
    • Cheng-Jun Hu
    • Ru-Hong Zhuo
    • Yue-Shan Lei
    • Na-Na Han
    • Liu He
  • View Affiliations

  • Published online on: October 10, 2014     https://doi.org/10.3892/mmr.2014.2624
  • Pages: 3003-3008
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Abstract

Following a limited number of cell divisions, mesenchymal stem cells (MSCs) undergo senescence, and these senescent cells maintain metabolic modification and remain viable for long periods. Autophagy, an intracellular bulk degradation process, provides a survival effect for cells under stress. In this study, the effect of autophagy on senescent MSCs was analyzed. Following serial passaging, rat MSCs underwent replicative senescence, characterized by positive staining for senescence-associated β-galactosidase (SA-β-gal), and increased expression levels of p16 and p21. During MSC senescence, the levels of autophagic activity were increased, a greater number of autophagic vacuoles were observed in senescent MSCs by transmission electron microscopy, acridine orange staining was elevated and the expression levels of autophagy‑related proteins (microtubule‑associated protein 1A/1B‑light chain 3-II, Atg7 and Atg12) were increased. The role of autophagy in MSC senescence was further investigated through pharmacological inhibition of autophagy with bafilomycin A1 and 3-methyladenine. Inhibition of autophagy by pharmacological means reduced the rate of positive staining for SA-β-gal and the expression levels of senescence‑related proteins. In conclusion, these findings suggest that autophagy is activated during senescence and the autophagic activity may be a requirement for maintaining the senescent state of MSCs.
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December-2014
Volume 10 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Zheng Y, Hu C, Zhuo R, Lei Y, Han N and He L: Inhibition of autophagy alleviates the senescent state of rat mesenchymal stem cells during long-term culture. Mol Med Rep 10: 3003-3008, 2014
APA
Zheng, Y., Hu, C., Zhuo, R., Lei, Y., Han, N., & He, L. (2014). Inhibition of autophagy alleviates the senescent state of rat mesenchymal stem cells during long-term culture. Molecular Medicine Reports, 10, 3003-3008. https://doi.org/10.3892/mmr.2014.2624
MLA
Zheng, Y., Hu, C., Zhuo, R., Lei, Y., Han, N., He, L."Inhibition of autophagy alleviates the senescent state of rat mesenchymal stem cells during long-term culture". Molecular Medicine Reports 10.6 (2014): 3003-3008.
Chicago
Zheng, Y., Hu, C., Zhuo, R., Lei, Y., Han, N., He, L."Inhibition of autophagy alleviates the senescent state of rat mesenchymal stem cells during long-term culture". Molecular Medicine Reports 10, no. 6 (2014): 3003-3008. https://doi.org/10.3892/mmr.2014.2624