Departmental Papers (Dental)
The Fas/Fap-1/Cav-1 complex regulates IL-1RA secretion in mesenchymal stem cells to accelerate wound healing
Date of this Version
Science Translational Medicine
Article number eaai8524
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-? (TNF-?) serves as an activator to up-regulate Fas and Fap-1 expression via the nuclear factor ?B 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. © 2018 The Authors, Some Rights Reserved.
Animals, Caveolin 1, fas Receptor, Female, Interleukin 1 Receptor Antagonist Protein, Mesenchymal Stem Cells, Mice, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Inbred MRL lpr, Mice, Knockout, Protein Tyrosine Phosphatase, Non-Receptor Type 13, Wound Healing, caveolin 1, Fas associated phosphatase 1, immunoglobulin enhancer binding protein, interleukin 1 receptor blocking agent, phosphatase, SNARE protein, tumor necrosis factor, tumor necrosis factor receptor superfamily member 6, unclassified drug, caveolin 1, Fas protein, mouse, interleukin 1 receptor blocking agent, non receptor protein tyrosine phosphatase 13, tumor necrosis factor receptor superfamily member 6, animal cell, animal experiment, Article, bone marrow, cell isolation, controlled study, CRISPR-CAS9 system, cytokine release, exosome, female, genetic transfection, gingiva, human, human cell, immunoprecipitation, mesenchymal stem cell, microscopy, mouse, nonhuman, plasmid, priority journal, protein binding, protein expression, regulatory mechanism, upregulation, Western blotting, wound healing, animal, C3H mouse, C57BL mouse, genetics, knockout mouse, mesenchymal stem cell, metabolism, Murphy Roths large lymphoproliferative mouse, physiology, wound healing
Kou, X., Xu, X., Chen, C., Sanmillan, M. L., Cai, T., Zhou, Y., Girauda, C., Le, A., & Shi, S. (2018). The Fas/Fap-1/Cav-1 complex regulates IL-1RA secretion in mesenchymal stem cells to accelerate wound healing. Science Translational Medicine, 10 (432), Article number eaai8524-. http://dx.doi.org/10.1126/scitranslmed.aai8524
Oral and Maxillofacial Surgery Commons, Oral Biology and Oral Pathology Commons, Orthodontics and Orthodontology Commons
Date Posted: 09 February 2023
This document has been peer reviewed.