Turner Christopher T, Bolsoni Juliana, Zeglinski Matthew R, Zhao Hongyan, Ponomarev Tatjana, Richardson Katlyn, Hiroyasu Sho, Schmid Erin, Papp Anthony, Granville David J
International Collaboration on Repair Discoveries (ICORD) Centre, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC, Canada.
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
NPJ Aging Mech Dis. 2021 Mar 5;7(1):6. doi: 10.1038/s41514-021-00059-6.
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.
压力性损伤（PIs），也被称为褥疮或压疮，是老年人死亡和发病的主要原因。丝氨酸蛋白酶颗粒酶B（GzmB）会导致皮肤老化和伤口愈合受损。衰老是发生压力性损伤的主要风险因素；因此，研究了GzmB在压力性损伤发病机制中的作用。人压力性损伤组织和伤口液中的GzmB水平显著升高。使用压力性损伤小鼠模型在GzmB基因敲除（GzmB-/-）和野生型（WT）小鼠中评估GzmB的致病作用。还利用载脂蛋白E基因敲除（ApoE-/-）的衰老和血管功能障碍模型，在更类似于老年人组织灌注的相关年龄相关模型中评估GzmB。年轻的GzmB-/-小鼠和WT小鼠之间的压力性损伤严重程度没有差异。然而，在老年小鼠中，缺乏GzmB的小鼠压力性损伤严重程度降低。从机制上讲，GzmB会增加血管壁炎症并损害细胞外基质重塑。总之，GzmB是年龄依赖性压力性损伤愈合受损的重要促成因素。
