| First Author | Kou X | Year | 2018 |
| Journal | Sci Transl Med | Volume | 10 |
| Issue | 432 | PubMed ID | 29540618 |
| Mgi Jnum | J:258813 | Mgi Id | MGI:6144400 |
| Doi | 10.1126/scitranslmed.aai8524 | Citation | Kou X, et al. (2018) The Fas/Fap-1/Cav-1 complex regulates IL-1RA secretion in mesenchymal stem cells to accelerate wound healing. Sci Transl Med 10(432) |
| abstractText | Mesenchymal stem cells (MSCs) are capable of secreting exosomes, extracellular vesicles, and cytokines to regulate cell and tissue homeostasis. However, it is unknown whether MSCs use a specific exocytotic fusion mechanism to secrete exosomes and cytokines. We show that Fas binds with Fas-associated phosphatase-1 (Fap-1) and caveolin-1 (Cav-1) to activate a common soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor (SNARE)-mediated membrane fusion mechanism to release small extracellular vesicles (sEVs) in MSCs. Moreover, we reveal that MSCs produce and secrete interleukin-1 receptor antagonist (IL-1RA) associated with sEVs to maintain rapid wound healing in the gingiva via the Fas/Fap-1/Cav-1 cascade. Tumor necrosis factor-alpha (TNF-alpha) serves as an activator to up-regulate Fas and Fap-1 expression via the nuclear factor kappaB pathway to promote IL-1RA release. This study identifies a previously unknown Fas/Fap-1/Cav-1 axis that regulates SNARE-mediated sEV and IL-1RA secretion in stem cells, which contributes to accelerated wound healing. |
