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Pubmed ID :30239625
Publication Date : //

Embryonic stem cell-derived mmu-miR-291a-3p inhibits cellular senescence in human dermal fibroblasts through the TGF--receptor 2 pathway.


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 miRNAs in conditioned medium (CM) via miRNA 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 TGFBR2, p53, and p21. Mmu-miR-291a-3p in CM was enclosed in ESC-derived exosomes and exosomes purified from ESC-CM inhibited cellular senescence. The inhibitory effects of mmu-miR-291a-3p were mediated through the TGFBR2 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.

Authors : 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 ,

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