PMID- 34837653
OWN - NLM
STAT- MEDLINE
DCOM- 20220128
LR  - 20220429
IS  - 1524-475X (Electronic)
IS  - 1067-1927 (Print)
IS  - 1067-1927 (Linking)
VI  - 30
IP  - 1
DP  - 2022 Jan
TI  - The lysosomal trafficking regulator is necessary for normal wound healing.
PG  - 82-99
LID - 10.1111/wrr.12984 [doi]
AB  - Non-healing wounds are a major threat to public health throughout the United 
      States. Tissue healing is complex multifactorial process that requires 
      synchronicity of several cell types. Endolysosomal trafficking, which contributes 
      to various cell functions from protein degradation to plasma membrane repair, is 
      an understudied process in the context of wound healing. The lysosomal 
      trafficking regulator protein (LYST) is an essential protein of the endolysosomal 
      system through an indeterminate mechanism. In this study, we examine the impact 
      of impaired LYST function both in vitro with primary LYST mutant fibroblasts as 
      well as in vivo with an excisional wound model. The wound model shows that LYST 
      mutant mice have impaired wound healing in the form of delayed epithelialization 
      and collagen deposition, independent of macrophage infiltration and polarisation. 
      We show that LYST mutation confers a deficit in MCP-1, IGF-1, and IGFBP-2 
      secretion in beige fibroblasts, which are critical factors in normal wound 
      healing. Identifying the mechanism of LYST function is important for 
      understanding normal wound biology, which may facilitate the development of 
      strategies to address problem wound healing.
CI  - (c) 2021 The Wound Healing Society.
FAU - Zbinden, Jacob C
AU  - Zbinden JC
AUID- ORCID: 0000-0002-0262-383X
AD  - Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide 
      Children's Hospital, Columbus, Ohio, USA.
AD  - Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio, 
      USA.
FAU - Mirhaidari, Gabriel J M
AU  - Mirhaidari GJM
AD  - Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide 
      Children's Hospital, Columbus, Ohio, USA.
AD  - Biomedical Sciences Graduate Program, The Ohio State University College of 
      Medicine, Columbus, Ohio, USA.
FAU - Blum, Kevin M
AU  - Blum KM
AD  - Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide 
      Children's Hospital, Columbus, Ohio, USA.
AD  - Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio, 
      USA.
FAU - Musgrave, Andrew J
AU  - Musgrave AJ
AD  - Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide 
      Children's Hospital, Columbus, Ohio, USA.
FAU - Reinhardt, James W
AU  - Reinhardt JW
AD  - Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide 
      Children's Hospital, Columbus, Ohio, USA.
FAU - Breuer, Christopher K
AU  - Breuer CK
AD  - Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide 
      Children's Hospital, Columbus, Ohio, USA.
FAU - Barker, Jenny C
AU  - Barker JC
AD  - Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide 
      Children's Hospital, Columbus, Ohio, USA.
AD  - Department of Plastic and Reconstructive Surgery, The Ohio State University 
      Wexner Medical Center, Columbus, Ohio, USA.
LA  - eng
GR  - F32 HL144120/HL/NHLBI NIH HHS/United States
GR  - R41 HL145827/HL/NHLBI NIH HHS/United States
GR  - R01 HL157491/HL/NHLBI NIH HHS/United States
GR  - R01 HL128847/HL/NHLBI NIH HHS/United States
GR  - R43 HL152844/HL/NHLBI NIH HHS/United States
GR  - T32 AI106704/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20211127
PL  - United States
TA  - Wound Repair Regen
JT  - Wound repair and regeneration : official publication of the Wound Healing Society 
      [and] the European Tissue Repair Society
JID - 9310939
RN  - 9007-34-5 (Collagen)
SB  - IM
MH  - Animals
MH  - Collagen
MH  - Fibroblasts
MH  - *Lysosomes
MH  - Mice
MH  - Re-Epithelialization
MH  - *Wound Healing
PMC - PMC9004365
MID - NIHMS1789836
OTO - NOTNLM
OT  - IGF-1
OT  - IGFBP-2
OT  - LYST
OT  - MCP-1
OT  - epithelialization
OT  - lysosomal trafficking regulator
OT  - wound healing
COIS- CONFLICT OF INTEREST Christopher K. Breuer is a founder of LYST Therapeutics, LLC 
      (OH, USA) and a portion of this work was supported by a sponsored research 
      agreement from LYST Therapeutics, LLC. The authors have no other relevant 
      affiliations or financial involvement with any organisation or entity with a 
      financial interest in or financial conflict with the subject matter or materials 
      discussed in the manuscript apart from those disclosed.
EDAT- 2021/11/28 06:00
MHDA- 2022/01/29 06:00
PMCR- 2022/04/12
CRDT- 2021/11/27 12:09
PHST- 2021/11/01 00:00 [revised]
PHST- 2021/06/07 00:00 [received]
PHST- 2021/11/09 00:00 [accepted]
PHST- 2021/11/28 06:00 [pubmed]
PHST- 2022/01/29 06:00 [medline]
PHST- 2021/11/27 12:09 [entrez]
PHST- 2022/04/12 00:00 [pmc-release]
AID - 10.1111/wrr.12984 [doi]
PST - ppublish
SO  - Wound Repair Regen. 2022 Jan;30(1):82-99. doi: 10.1111/wrr.12984. Epub 2021 Nov 
      27.