Autophagy Prevents Oxidative Stress-Induced Loss of Self-Renewal Capacity and Stemness in Human Tendon Stem Cells by Reducing ROS Accumulation
Background/Aims: Tendon stem cells (TSCs) exhibit a high self-renewal capacity, multi-differentiation potential, and low immunogenicity; thus, these cells might provide a new cell source for tendon repair and regeneration. TSCs are exposed to increased oxidative stress at tendon injury sites; howeve...
Saved in:
Published in | Cellular physiology and biochemistry Vol. 39; no. 6; pp. 2227 - 2238 |
---|---|
Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Basel, Switzerland
Cell Physiol Biochem Press GmbH & Co KG
01.01.2016
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Background/Aims: Tendon stem cells (TSCs) exhibit a high self-renewal capacity, multi-differentiation potential, and low immunogenicity; thus, these cells might provide a new cell source for tendon repair and regeneration. TSCs are exposed to increased oxidative stress at tendon injury sites; however, how TSCs maintain their stemness under oxidative stress is not clear. Methods and Results: In this study, we found that H 2 O 2 treatment increased ROS accumulation in human TSCs (hTSCs) and resulted in loss of self-renewal capacity and stemness, as reflected in reduced colony formation and proliferation, decreased expression of the stemness markers Nanog, Oct-4, NS, and SSEA-4, and impaired differentiation capability. These H 2 O 2 -induced damages were prevented by pretreatment with starvation or rapamycin. Pretreatment with starvation or rapamycin prior to H 2 O 2 exposure also led to decreased intracellular and mitochondrial ROS accumulation along with increased autophagic activity, as manifested in increased LC3 cleavage, Beclin-1 expression, and GFP-LC3-labeled autophagosome formation. Autophagy inhibition by 3-MA or CQ, or by shRNA silencing of Agt-7 or Beclin-1 reduced the protective effects of starvation and rapamycin on H 2 O 2 -treated hTSCs. Conclusion: Thus, the findings of this study suggest that autophagy prevents oxidative stress-induced loss of self-renewal capacity and stemness in hTSCs through suppression of ROS accumulation. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1015-8987 1421-9778 |
DOI: | 10.1159/000447916 |