Free Radical Biology and Medicine
Free Radical Biology and Medicine
5 years ago

EphB2 signaling-mediated Sirt3 expression reduces MSC senescence by maintaining mitochondrial ROS homeostasis

EphB2 signaling-mediated Sirt3 expression reduces MSC senescence by maintaining mitochondrial ROS homeostasis
Disruption of mitochondrial reactive oxygen species (mtROS) homeostasis is a key factor inducing UCB-MSC senescence. Accordingly, preventing mtROS accumulation will help in suppressing the UCB-MSC senescence. In this study, we observed that the expressions of EphrinB2 and EphB2 were inversely regulated by UCB-MSC passage-dependent manner. EphB2 signaling induced mitochondrial translocation of Sirt3. The knockdown of SIRT3 inhibited the effect of EphB2 signaling in UCB-MSCs. Subsequently, EphrinB2-Fc induced the nuclear translocation of Nrf-2 via c-Src phosphorylation dependent manner, and Sirt3 expression was regulated by Nrf-2. Among Sirt3 target genes, EphB2 signaling increased MnSOD and reduced the mtROS level in UCB-MSCs. Furthermore, the deacetylase effect of Sirt3 enhanced the MnSOD activity by deacetylation at the lysine 68 residue and therapeutic effect of UCB-MSCs on skin-wound healing was increased by EphB2 activation. In conclusion, the EphB2 can serve as a novel target for the optimizing the therapeutic use of UCB-MSCs in wound repair by MnSOD-mediated mtROS scavenging through EphB2/c-Src signaling pathway and Nrf-2-dependent Sirt3 expression.

Publisher URL: www.sciencedirect.com/science

DOI: S0891584917306731

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.