PMID- 29540618
OWN - NLM
STAT- MEDLINE
DCOM- 20190923
LR  - 20240420
IS  - 1946-6242 (Electronic)
IS  - 1946-6234 (Print)
IS  - 1946-6234 (Linking)
VI  - 10
IP  - 432
DP  - 2018 Mar 14
TI  - The Fas/Fap-1/Cav-1 complex regulates IL-1RA secretion in mesenchymal stem cells 
      to accelerate wound healing.
LID - 10.1126/scitranslmed.aai8524 [doi]
LID - eaai8524
AB  - 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.
CI  - Copyright (c) 2018 The Authors, some rights reserved; exclusive licensee American 
      Association for the Advancement of Science. No claim to original U.S. Government 
      Works.
FAU - Kou, Xiaoxing
AU  - Kou X
AUID- ORCID: 0000-0001-9680-0077
AD  - Department of Anatomy and Cell Biology, University of Pennsylvania School of 
      Dental Medicine, Philadelphia, PA 19104, USA.
AD  - Department of Orthodontics, Peking University School and Hospital of Stomatology, 
      #22 Zhongguancun South Avenue, Beijing 100081, China.
FAU - Xu, Xingtian
AU  - Xu X
AD  - Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University 
      of Southern California, 2250 Alcazar Street, CSA 103, Los Angeles, CA 90033, USA.
FAU - Chen, Chider
AU  - Chen C
AUID- ORCID: 0000-0003-2899-1208
AD  - Department of Anatomy and Cell Biology, University of Pennsylvania School of 
      Dental Medicine, Philadelphia, PA 19104, USA.
FAU - Sanmillan, Maria Laura
AU  - Sanmillan ML
AD  - Department of Pathology and Laboratory Medicine, Children's Hospital of 
      Philadelphia, University of Pennsylvania, Philadelphia, PA 19104, USA.
FAU - Cai, Tao
AU  - Cai T
AUID- ORCID: 0000-0002-2877-8637
AD  - National Institute of Dental and Craniofacial Research, National Institutes of 
      Health, Bethesda, MD 20982, USA.
FAU - Zhou, Yanheng
AU  - Zhou Y
AD  - Department of Orthodontics, Peking University School and Hospital of Stomatology, 
      #22 Zhongguancun South Avenue, Beijing 100081, China.
FAU - Giraudo, Claudio
AU  - Giraudo C
AD  - Department of Pathology and Laboratory Medicine, Children's Hospital of 
      Philadelphia, University of Pennsylvania, Philadelphia, PA 19104, USA.
FAU - Le, Anh
AU  - Le A
AUID- ORCID: 0000-0003-4726-2529
AD  - Department of Anatomy and Cell Biology, University of Pennsylvania School of 
      Dental Medicine, Philadelphia, PA 19104, USA.
FAU - Shi, Songtao
AU  - Shi S
AD  - Department of Anatomy and Cell Biology, University of Pennsylvania School of 
      Dental Medicine, Philadelphia, PA 19104, USA. songtaos@upenn.edu.
LA  - eng
GR  - R01 DE017449/DE/NIDCR NIH HHS/United States
GR  - R03 DE028026/DE/NIDCR NIH HHS/United States
GR  - K99 DE025915/DE/NIDCR NIH HHS/United States
GR  - R00 DE025915/DE/NIDCR NIH HHS/United States
GR  - R01 DE019932/DE/NIDCR NIH HHS/United States
GR  - R01 GM123020/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Sci Transl Med
JT  - Science translational medicine
JID - 101505086
RN  - 0 (Caveolin 1)
RN  - 0 (Fas protein, mouse)
RN  - 0 (Interleukin 1 Receptor Antagonist Protein)
RN  - 0 (fas Receptor)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 13)
SB  - IM
MH  - Animals
MH  - Caveolin 1/genetics/*metabolism
MH  - Female
MH  - Interleukin 1 Receptor Antagonist Protein/*metabolism
MH  - Mesenchymal Stem Cells/*metabolism
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred MRL lpr
MH  - Mice, Knockout
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 13/genetics/*metabolism
MH  - Wound Healing/genetics/physiology
MH  - fas Receptor/genetics/*metabolism
PMC - PMC6310133
MID - NIHMS969162
COIS- Competing interests: The authors declare that they have no competing interests.
EDAT- 2018/03/16 06:00
MHDA- 2019/09/24 06:00
PMCR- 2018/12/28
CRDT- 2018/03/16 06:00
PHST- 2016/08/22 00:00 [received]
PHST- 2017/03/06 00:00 [revised]
PHST- 2018/02/13 00:00 [accepted]
PHST- 2018/03/16 06:00 [entrez]
PHST- 2018/03/16 06:00 [pubmed]
PHST- 2019/09/24 06:00 [medline]
PHST- 2018/12/28 00:00 [pmc-release]
AID - 10/432/eaai8524 [pii]
AID - 10.1126/scitranslmed.aai8524 [doi]
PST - ppublish
SO  - Sci Transl Med. 2018 Mar 14;10(432):eaai8524. doi: 10.1126/scitranslmed.aai8524.