Stem Cell-Derived Exosomes Prevent Aging-Induced Cardiac Dysfunction through a Novel Exosome/lncRNA MALAT1/NF- κ B/TNF- α Signaling Pathway

Oxid Med Cell Longev. 2019 Apr 8:2019:9739258. doi: 10.1155/2019/9739258. eCollection 2019.

Abstract

Aging is a risk factor for cardiovascular disease, and there is no effective therapeutic approach to alleviate this condition. NF-κB and TNF-α have been implicated in the activation of the aging process, but the signaling molecules responsible for the inactivation of NF-κB and TNF-α remain unknown. Exosomes have been reported to improve heart functions by releasing miRNA. Recent studies suggest that lncRNAs are more tissue-specific and developmental stage-specific compared to miRNA. However, the role of lncRNA in exosome-mediated cardiac repair has not been explored. In the present study, we focused on metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), which is an lncRNA associated with cell senescence. We discovered that human umbilical cord mesenchymal stem cell- (UMSC-) derived exosomes prevent aging-induced cardiac dysfunction. Silencer RNA against lncRNA MALAT1 blocked the beneficial effects of exosomes. In summary, we discovered that UMSC-derived exosomes prevent aging-induced cardiac dysfunction by releasing novel lncRNA MALAT1, which in turn inhibits the NF-κB/TNF-α signaling pathway. These findings will lead to the development of therapies that delay aging and progression of age-related diseases.

MeSH terms

  • Aging / metabolism*
  • Animals
  • Cellular Senescence
  • Exosomes / metabolism*
  • Heart / physiopathology*
  • Humans
  • Hydrogen Peroxide / toxicity
  • Male
  • Mesenchymal Stem Cells / metabolism*
  • Mice, Inbred C57BL
  • Models, Biological
  • NF-kappa B / metabolism*
  • RNA, Long Noncoding / metabolism*
  • Rats
  • Signal Transduction*
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • MALAT1 long non-coding RNA, human
  • NF-kappa B
  • RNA, Long Noncoding
  • Tumor Necrosis Factor-alpha
  • Hydrogen Peroxide