Cutaneous Wounds in Mice Lacking TSG-6 Exhibit Delayed Closure and an Abnormal Inflammatory Response.
Journal
The Journal of investigative dermatology
ISSN: 1523-1747
Titre abrégé: J Invest Dermatol
Pays: United States
ID NLM: 0426720
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
04
06
2019
revised:
12
04
2020
accepted:
17
04
2020
pubmed:
19
5
2020
medline:
2
4
2021
entrez:
19
5
2020
Statut:
ppublish
Résumé
We investigated how loss of TSG-6 affects wound closure and skin inflammation. TSG-6 has several known biological functions, including the enzymatic transfer of heavy-chain proteins from inter-α-trypsin inhibitor to hyaluronan to form heavy-chain protein-hyaluronan complexes. TSG-6 and heavy-chain protein-hyaluronan are constitutively expressed in normal skin and increase post-wounding but are completely absent in TSG-6-null mice. Wound closure rates are significantly delayed in TSG-6-null mice relative to wildtype mice. Neutrophil recruitment is delayed in early wounds (12 hours and day 1), whereas late wounds (day 7) show elevated neutrophil accumulation. In addition, granulation phase resolution is delayed, with persistent blood vessels and reduced dermal collagen at 10 days. The proinflammatory cytokine TNFα is elevated >3-fold in unwounded TSG-6-null skin and increases further after wounding (from 12 hours to 7 days) before returning to baseline by day 10. Other cytokines examined, such as IL-6, IL-10, and monocyte chemotactic protein-1, showed no consistent differences. Reintroduction of TSG-6 into TSG-6-null wounds rescues both the delay in wound closure and the aberrant neutrophil phenotype. In summary, our study indicates that TSG-6 plays an important role in regulating wound closure and inflammation during cutaneous wound repair.
Identifiants
pubmed: 32422216
pii: S0022-202X(20)31574-8
doi: 10.1016/j.jid.2020.04.015
pmc: PMC7749718
mid: NIHMS1613257
pii:
doi:
Substances chimiques
Cell Adhesion Molecules
0
Tnf protein, mouse
0
Tnfaip6 protein, mouse
0
Tumor Necrosis Factor-alpha
0
Hyaluronic Acid
9004-61-9
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2505-2514Subventions
Organisme : NHLBI NIH HHS
ID : P01 HL107147
Pays : United States
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Références
Invest Ophthalmol Vis Sci. 2014 Jul 17;55(8):4905-12
pubmed: 25034606
Eur J Pharmacol. 2015 Mar 15;751:42-9
pubmed: 25661977
J Biol Chem. 2016 Jun 10;291(24):12627-40
pubmed: 27044744
Gastroenterology. 2015 Jul;149(1):163-176.e20
pubmed: 25790743
J Biol Chem. 2013 Sep 6;288(36):25792-803
pubmed: 23878196
Cell Stem Cell. 2009 Jul 2;5(1):54-63
pubmed: 19570514
J Biol Chem. 2013 Jan 4;288(1):412-22
pubmed: 23118230
Adv Wound Care (New Rochelle). 2013 Sep;2(7):379-388
pubmed: 24527354
Proc Natl Acad Sci U S A. 2010 Sep 28;107(39):16875-80
pubmed: 20837529
J Cell Sci. 2003 May 15;116(Pt 10):1863-73
pubmed: 12692188
Pflugers Arch. 2007 Jun;454(3):345-59
pubmed: 17256154
Gene. 1997 Nov 20;202(1-2):95-102
pubmed: 9427551
Reproduction. 2003 Jan;125(1):27-31
pubmed: 12622693
J Eur Acad Dermatol Venereol. 2011 Mar;25(3):317-27
pubmed: 20642475
J Periodontol. 2015 Jan;86(1):62-71
pubmed: 25269522
Cell Tissue Res. 2018 Mar;371(3):531-539
pubmed: 29383445
J Immunol. 1993 Dec 1;151(11):6593-601
pubmed: 8245487
Am J Pathol. 2001 Nov;159(5):1711-21
pubmed: 11696432
Arthritis Rheum. 2004 Sep;50(9):3012-22
pubmed: 15457471
N Engl J Med. 1999 Sep 2;341(10):738-46
pubmed: 10471461
Proc Natl Acad Sci U S A. 2016 Dec 13;113(50):E8151-E8158
pubmed: 27911817
J Biol Chem. 2005 Jul 8;280(27):25674-86
pubmed: 15840581
J Biol Chem. 2006 Jul 21;281(29):20303-14
pubmed: 16702221
J Invest Dermatol. 2014 Feb;134(2):526-537
pubmed: 23921952
J Immunol. 2014 Mar 1;192(5):2177-85
pubmed: 24501198
Hum Reprod Update. 1999 Jul-Aug;5(4):293-301
pubmed: 10465521
J Biol Chem. 2009 Jan 23;284(4):2320-31
pubmed: 19033448
Wound Repair Regen. 2008 Sep-Oct;16(5):585-601
pubmed: 19128254
Microcirculation. 2004 Oct-Nov;11(7):615-24
pubmed: 15513871
Development. 2003 May;130(10):2253-61
pubmed: 12668637
J Invest Dermatol. 2017 Apr;137(4):941-950
pubmed: 28017830
Science. 1997 Apr 4;276(5309):75-81
pubmed: 9082989
Trends Cell Biol. 2005 Nov;15(11):599-607
pubmed: 16202600
Methods Mol Biol. 2015;1229:543-8
pubmed: 25325979
J Invest Dermatol. 2008 Jul;128(7):1812-20
pubmed: 18185533
Int J Cell Biol. 2015;2015:701738
pubmed: 26448756
J Biol Chem. 2014 Mar 7;289(10):6791-8
pubmed: 24403074
J Biol Chem. 2002 Dec 27;277(52):51068-76
pubmed: 12401803
J Biol Chem. 2004 Mar 19;279(12):11119-28
pubmed: 14707130
Mol Cell Biol. 1990 May;10(5):1982-8
pubmed: 2183014
Ann N Y Acad Sci. 2001;936:355-67
pubmed: 11460492