ANT2 Accelerates Cutaneous Wound Healing in Aged Skin by Regulating Energy Homeostasis and Inflammation

被引:7
|
作者
Woo, Seung-Hwa [1 ]
Mo, Yun Jeong [2 ]
Lee, Yun-Il [2 ]
Park, Ji Hwan [1 ]
Hwang, Daehee [3 ]
Park, Tae Jun [4 ,5 ]
Kang, Hee Young [5 ,6 ]
Park, Sang Chul [7 ]
Lee, Young -Sam [1 ]
机构
[1] Daegu Gyeongbuk Inst Sci & Technol DGIST, Dept New Biol, 333 Technojungang Dareo, Daegu 42988, South Korea
[2] Daegu Gyeongbuk Inst Sci & Technol DGIST, Well Aging Res Ctr, Div Biotechnol, Daegu, South Korea
[3] Seoul Natl Univ, Dept Biol Sci, Seoul, South Korea
[4] Ajou Univ, Sch Med, Dept Biochem & Mol Biol, Suwon, South Korea
[5] Ajou Univ, Sch Med, Translat Res Ctr, Inst Inflamm Aging, Suwon, South Korea
[6] Ajou Univ, Sch Med, Dept Dermatol, Suwon, South Korea
[7] Chonnam Natl Univ, Adv Inst Aging Sci, Future Life & Soc Res Ctr, Gwangju, South Korea
基金
新加坡国家研究基金会;
关键词
CELLULAR SENESCENCE; MITOCHONDRIAL PROTEIN; DERMAL FIBROBLASTS; DNA-DAMAGE; STEM-CELLS; CANCER; PROLIFERATION; MIGRATION; DELIVERY; HSP70;
D O I
10.1016/j.jid.2023.05.002
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
An effective healing response is critical to healthy aging. In particular, energy homeostasis has become increasingly recognized as a factor in effective skin regeneration. ANT2 is a mediator of adenosine triphosphate import into mitochondria for energy homeostasis. Although energy homeostasis and mitochondrial integrity are critical for wound healing, the role played by ANT2 in the repair process had not been elucidated to date. In our study, we found that ANT2 expression decreased in aged skin and cellular senescence. Interestingly, overexpression of ANT2 in aged mouse skin accelerated the healing of full-thickness cutaneous wounds. In addition, upregulation of ANT2 in replicative senescent human diploid dermal fibroblasts induced their proliferation and migration, which are critical processes in wound healing. Regarding energy homeostasis, ANT2 overexpression increased the adenosine triphosphate production rate by activating glycolysis and induced mitophagy. Notably, ANT2-mediated upregulation of HSPA6 in aged human diploid dermal fibroblasts downregulated proinflammatory genes that mediate cellular senescence and mitochondrial damage. This study shows a previously uncharacterized physiological role of ANT2 in skin wound healing by regulating cell proliferation, energy homeostasis, and inflammation. Thus, our study links energy metabolism to skin homeostasis and reports, to the best of our knowledge, a previously unreported genetic factor that enhances wound healing in an aging model.
引用
收藏
页码:2295 / +
页数:33
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