PMID- 36056472
OWN - NLM
STAT- MEDLINE
DCOM- 20230323
LR  - 20230324
IS  - 1742-481X (Electronic)
IS  - 1742-4801 (Print)
IS  - 1742-4801 (Linking)
VI  - 20
IP  - 4
DP  - 2023 Apr
TI  - TSG-6 inhibits hypertrophic scar fibroblast proliferation by regulating 
      IRE1alpha/TRAF2/NF-kappaB signalling.
PG  - 1008-1019
LID - 10.1111/iwj.13950 [doi]
AB  - TNF-stimulated gene (TSG-6) was reported to suppress hypertrophic scar (HS) 
      formation in a rabbit ear model, and the overexpression of TSG-6 in human HS 
      fibroblasts (HSFs) was found to induce their apoptotic death. The molecular basis 
      for these findings, however, remains to be clarified. HSFs were subjected to 
      TSG-6 treatment. Treatment with TSG-6 significantly suppressed HSF proliferation 
      and induced them to undergo apoptosis. Moreover, TSG-6 exposure led to reductions 
      in collagen I, collagen III, and alpha-SMA mRNA and protein levels, with a 
      corresponding drop in proliferating cell nuclear antigen (PCNA) expression 
      indicative of impaired proliferative activity. Endoplasmic reticulum (ER) stress 
      was also suppressed in these HSFs as demonstrated by decreases in Bip and p-IRE1alpha 
      expression, downstream inositol requiring enzyme 1 alpha (IRE1alpha) -Tumor necrosis 
      factor receptor associated factor 2 (TRAF2) pathway signalling was inhibited and 
      treated cells failed to induce NF-kappaB, TNF-alpha, IL-1beta, and IL-6 expression. Overall, 
      ER stress was found to trigger inflammatory activity in HSFs via the IRE1alpha-TRAF2 
      axis, as confirmed with the specific inhibitor of IRE1alpha STF083010. Additionally, 
      the effects of TSG-6 on apoptosis, collagen I, collagen III, alpha-SMA, and PCNA of 
      HSFs were reversed by the IRE1alpha activator thapsigargin (TG). These data suggest 
      that TSG-6 administration can effectively suppress the proliferation of HSFs in 
      part via the inhibition of IRE1alpha-mediated ER stress-induced inflammation 
      (IRE1alpha/TRAF2/NF-kappaB signalling).
CI  - (c) 2022 The Authors. International Wound Journal published by Medicalhelplines.com 
      Inc (3M) and John Wiley & Sons Ltd.
FAU - Ma, Li
AU  - Ma L
AD  - Clinical College of Integrated Traditional Chinese and Western Medicine, Anhui 
      University of Traditional Chinese Medicine, Hefei, China.
FAU - Hua, Lei
AU  - Hua L
AD  - Department of Neurology, the Affiliated Nanjing city Hospital of Chinese Medicine 
      of Nanjing University of Chinese Medicine, Nanjing, China.
FAU - Yu, Wenyuan
AU  - Yu W
AD  - Department of Plastic and Cosmetic Surgery, the Second Affiliated Hospital of 
      Soochow University, SuZhou City, PR China.
FAU - Ke, Li
AU  - Ke L
AD  - Department of Thoracic Surgery, the First Affiliated Hospital of University of 
      Science and Technology of China (Anhui Provincial Hospital), Hefei, China.
FAU - Li, Liang-Yong
AU  - Li LY
AUID- ORCID: 0000-0002-4241-5592
AD  - Department of Neurology, the First Affiliated Hospital of Anhui University of 
      Traditional Chinese Medicine, Hefei, China.
LA  - eng
GR  - KJ2017A286/the Natural Science Research Foundation of Colleges and Universities 
      in Anhui Province/
GR  - 1908085MH250/Natural Science Foundation of Anhui Province/
PT  - Journal Article
DEP - 20220902
PL  - England
TA  - Int Wound J
JT  - International wound journal
JID - 101230907
RN  - 0 (NF-kappa B)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - 0 (Proliferating Cell Nuclear Antigen)
RN  - EC 3.1.- (Endoribonucleases)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Rabbits
MH  - *NF-kappa B
MH  - Protein Serine-Threonine Kinases/metabolism/pharmacology
MH  - TNF Receptor-Associated Factor 2/metabolism/pharmacology
MH  - Proliferating Cell Nuclear Antigen/metabolism/pharmacology
MH  - *Cicatrix, Hypertrophic/metabolism
MH  - Endoribonucleases/metabolism/pharmacology
MH  - Fibroblasts
MH  - Cell Proliferation
PMC - PMC10031217
OTO - NOTNLM
OT  - IRE1alpha
OT  - TSG-6
OT  - endoplasmic reticulum stress
OT  - hypertrophic scar fibroblasts
OT  - inflammation
COIS- The authors declare that there are no competing interests associated with the 
      manuscript.
EDAT- 2022/09/04 06:00
MHDA- 2023/03/24 06:00
PMCR- 2022/09/02
CRDT- 2022/09/03 00:52
PHST- 2022/08/17 00:00 [revised]
PHST- 2022/07/25 00:00 [received]
PHST- 2022/08/22 00:00 [accepted]
PHST- 2022/09/04 06:00 [pubmed]
PHST- 2023/03/24 06:00 [medline]
PHST- 2022/09/03 00:52 [entrez]
PHST- 2022/09/02 00:00 [pmc-release]
AID - IWJ13950 [pii]
AID - 10.1111/iwj.13950 [doi]
PST - ppublish
SO  - Int Wound J. 2023 Apr;20(4):1008-1019. doi: 10.1111/iwj.13950. Epub 2022 Sep 2.