Granzyme B mediates impaired healing of pressure injuries in aged skin

Abstract Pressure injuries (PIs), also known as bedsores or pressure ulcers, are a major cause of death and morbidity in the elderly. The serine protease, Granzyme B (GzmB), contributes to skin aging and impaired wound healing. Aging is a major risk factor for PIs; thus, the role of GzmB in PI patho...

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Autores principales:	Christopher T. Turner, Juliana Bolsoni, Matthew R. Zeglinski, Hongyan Zhao, Tatjana Ponomarev, Katlyn Richardson, Sho Hiroyasu, Erin Schmid, Anthony Papp, David J. Granville
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Geriatrics RC952-954.6
Acceso en línea:	https://doaj.org/article/1cca516d620c420db57294396d6eb6a8
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spelling	oai:doaj.org-article:1cca516d620c420db57294396d6eb6a82021-12-02T11:35:51ZGranzyme B mediates impaired healing of pressure injuries in aged skin10.1038/s41514-021-00059-62056-3973https://doaj.org/article/1cca516d620c420db57294396d6eb6a82021-03-01T00:00:00Zhttps://doi.org/10.1038/s41514-021-00059-6https://doaj.org/toc/2056-3973Abstract Pressure injuries (PIs), also known as bedsores or pressure ulcers, are a major cause of death and morbidity in the elderly. The serine protease, Granzyme B (GzmB), contributes to skin aging and impaired wound healing. Aging is a major risk factor for PIs; thus, the role of GzmB in PI pathogenesis was investigated. GzmB levels in human PI tissue and wound fluids were markedly elevated. A causative role for GzmB was assessed in GzmB knockout (GzmB−/−) and wild-type (WT) mice using a murine model of PI. An apolipoprotein E knockout (ApoE−/−) model of aging and vascular dysfunction was also utilized to assess GzmB in a relevant age-related model better resembling tissue perfusion in the elderly. PI severity displayed no difference between young GzmB−/− and WT mice. However, in aged mice, PI severity was reduced in mice lacking GzmB. Mechanistically, GzmB increased vascular wall inflammation and impaired extracellular matrix remodeling. Together, GzmB is an important contributor to age-dependent impaired PI healing.Christopher T. TurnerJuliana BolsoniMatthew R. ZeglinskiHongyan ZhaoTatjana PonomarevKatlyn RichardsonSho HiroyasuErin SchmidAnthony PappDavid J. GranvilleNature PortfolioarticleGeriatricsRC952-954.6ENnpj Aging and Mechanisms of Disease, Vol 7, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Geriatrics RC952-954.6
spellingShingle	Geriatrics RC952-954.6 Christopher T. Turner Juliana Bolsoni Matthew R. Zeglinski Hongyan Zhao Tatjana Ponomarev Katlyn Richardson Sho Hiroyasu Erin Schmid Anthony Papp David J. Granville Granzyme B mediates impaired healing of pressure injuries in aged skin
description	Abstract Pressure injuries (PIs), also known as bedsores or pressure ulcers, are a major cause of death and morbidity in the elderly. The serine protease, Granzyme B (GzmB), contributes to skin aging and impaired wound healing. Aging is a major risk factor for PIs; thus, the role of GzmB in PI pathogenesis was investigated. GzmB levels in human PI tissue and wound fluids were markedly elevated. A causative role for GzmB was assessed in GzmB knockout (GzmB−/−) and wild-type (WT) mice using a murine model of PI. An apolipoprotein E knockout (ApoE−/−) model of aging and vascular dysfunction was also utilized to assess GzmB in a relevant age-related model better resembling tissue perfusion in the elderly. PI severity displayed no difference between young GzmB−/− and WT mice. However, in aged mice, PI severity was reduced in mice lacking GzmB. Mechanistically, GzmB increased vascular wall inflammation and impaired extracellular matrix remodeling. Together, GzmB is an important contributor to age-dependent impaired PI healing.
format	article
author	Christopher T. Turner Juliana Bolsoni Matthew R. Zeglinski Hongyan Zhao Tatjana Ponomarev Katlyn Richardson Sho Hiroyasu Erin Schmid Anthony Papp David J. Granville
author_facet	Christopher T. Turner Juliana Bolsoni Matthew R. Zeglinski Hongyan Zhao Tatjana Ponomarev Katlyn Richardson Sho Hiroyasu Erin Schmid Anthony Papp David J. Granville
author_sort	Christopher T. Turner
title	Granzyme B mediates impaired healing of pressure injuries in aged skin
title_short	Granzyme B mediates impaired healing of pressure injuries in aged skin
title_full	Granzyme B mediates impaired healing of pressure injuries in aged skin
title_fullStr	Granzyme B mediates impaired healing of pressure injuries in aged skin
title_full_unstemmed	Granzyme B mediates impaired healing of pressure injuries in aged skin
title_sort	granzyme b mediates impaired healing of pressure injuries in aged skin
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1cca516d620c420db57294396d6eb6a8
work_keys_str_mv	AT christophertturner granzymebmediatesimpairedhealingofpressureinjuriesinagedskin AT julianabolsoni granzymebmediatesimpairedhealingofpressureinjuriesinagedskin AT matthewrzeglinski granzymebmediatesimpairedhealingofpressureinjuriesinagedskin AT hongyanzhao granzymebmediatesimpairedhealingofpressureinjuriesinagedskin AT tatjanaponomarev granzymebmediatesimpairedhealingofpressureinjuriesinagedskin AT katlynrichardson granzymebmediatesimpairedhealingofpressureinjuriesinagedskin AT shohiroyasu granzymebmediatesimpairedhealingofpressureinjuriesinagedskin AT erinschmid granzymebmediatesimpairedhealingofpressureinjuriesinagedskin AT anthonypapp granzymebmediatesimpairedhealingofpressureinjuriesinagedskin AT davidjgranville granzymebmediatesimpairedhealingofpressureinjuriesinagedskin
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Granzyme B mediates impaired healing of pressure injuries in aged skin

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