Details

Autor(en) / Beteiligte

• Bae, Yun-Ui
• Son, Youlim
• Kim, Chang-Hyun
• Kim, Kwang Seok
• Hyun, Se Hee
• Woo, Hyun Goo
• Jee, Byul A
• Choi, Jun-Hyuk
• Sung, Hoon-Ki
• Choi, Hyung-Chul
• Park, So Young
• Bae, Ju-Hyun
• Doh, Kyung-Oh
• Kim, Jae-Ryong
• Beerman, Isabel
• Hare, Joshua

Titel

Embryonic Stem Cell–Derived mmu-miR-291a-3p Inhibits Cellular Senescence in Human Dermal Fibroblasts Through the TGF-β Receptor 2 Pathway

Ist Teil von

• The journals of gerontology. Series A, Biological sciences and medical sciences, 2019-08, Vol.74 (9), p.1359-1367

Ort / Verlag

US: Oxford University Press

Erscheinungsjahr

2019

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Abstract Senescent cells accumulate in various tissues over time and contribute to tissue dysfunction and aging-associated phenotypes. Accumulating evidence suggests that cellular senescence can be inhibited through pharmacological intervention, as well as through treatment with soluble factors derived from embryonic stem cells (ESCs). In an attempt to investigate the anti-senescence factors secreted by ESCs, we analyzed mouse ESC-derived extracellular microRNAs in conditioned medium via microRNA array analysis. We selected mmu-miR-291a-3p as a putative anti-senescence factor via bioinformatics analysis. We validated its inhibitory effects on replicative, Adriamycin-induced, and ionizing radiation–induced senescence in human dermal fibroblasts. Treatment of senescent cells with mmu-miR-291a-3p decreased senescence-associated β-galactosidase activity, enhanced proliferative potential, and reduced mRNA and protein expression of TGF-β receptor 2, p53, and p21. mmu-miR-291a-3p in conditioned medium was enclosed in ESC-derived exosomes and exosomes purified from ESC conditioned medium inhibited cellular senescence. The inhibitory effects of mmu-miR-291a-3p were mediated through the TGF-β receptor 2 signaling pathway. Hsa-miR-371a-3p and hsa-miR-520e, the human homologs of mmu-miR-291a-3p, showed similar anti-senescence activity. Furthermore, mmu-miR-291a-3p accelerated the excisional skin wound healing process in aged mice. Our results indicate that the ESC-derived mmu-miR-291a-3p is a novel candidate agent that can be utilized for cell-free therapeutic intervention against aging and aging-related diseases.