1. miRNA-146a-5p mitigates stress-induced premature senescence of D-galactose-induced primary thymic stromal cells.
- Author
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Du H, Wang Y, Liu X, Wang S, Wu S, Yuan Z, and Zhu X
- Subjects
- Animals, Apoptosis drug effects, Apoptosis genetics, Cell Survival drug effects, Cell Survival genetics, Cells, Cultured, Cellular Senescence genetics, Cellular Senescence physiology, Gene Expression Regulation, Mice, Inbred C57BL, Primary Cell Culture, Reactive Oxygen Species metabolism, Stromal Cells metabolism, TNF Receptor-Associated Factor 6 genetics, TNF Receptor-Associated Factor 6 metabolism, Thymus Gland cytology, Mice, Cellular Senescence drug effects, Galactose pharmacology, MicroRNAs genetics, Oxidative Stress physiology, Stromal Cells drug effects
- Abstract
Senescent thymic stromal cells (TSCs) producing senescence-associated secretory phenotype (SASP) may play a role at later phases of thymic involution. However, the etiology and mechanisms responsible for TSC senescence remain to be elucidated. In the present study, the effects of oxidative stress on TSCs and role of miRNA-146a-5p in stress-induced premature senescence (SIPS) were identified. D-galactose (D-gal) induced oxidative stress in primary TSCs and a limited cumulative oxidative stress induced premature senescence but not apoptosis of TSCs. miRNA-146a-5p overexpression can mitigate the SIPS by targeting tumor necrosis factor receptor-associated factor 6 (TRAF6) instead of increasing autophagy clearance. Furthermore, exogenous miRNA-146a-5p reversed the upregulation of chemokines including Cxcl5, pro-inflammatory cytokines, and antimicrobial peptides in TSCs with SIPS. In conclusion, the accumulated oxidative stress may be partially responsible for senescence in TSCs and modulation of miRNA-146a-5p may attenuate this process., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2021
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