Improving dermal fibroblast-to-epidermis communications and aging wound repair through extracellular vesicle-mediated delivery of Gstm2 mRNA.

Publisher: BioMed Central Country of Publication: England NLM ID: 101152208 Publication Model: Electronic Cited Medium: Internet ISSN: 1477-3155 (Electronic) Linking ISSN: 14773155 NLM ISO Abbreviation: J Nanobiotechnology Subsets: MEDLINE

Original Publication: London : BioMed Central, 2003-

Wound Healing* ; Fibroblasts*/metabolism ; Glutathione Transferase*/metabolism ; Extracellular Vesicles*/metabolism ; RNA, Messenger*/metabolism ; RNA, Messenger*/genetics ; Skin Aging*; Animals ; Mice ; Epidermis/metabolism ; Mice, Inbred C57BL ; Oxidative Stress ; Skin/metabolism ; Male ; Humans ; Epidermal Cells/metabolism ; Cells, Cultured

Skin aging is characterized by the disruption of skin homeostasis and impaired skin injury repair. Treatment of aging skin has long been limited by the unclear intervention targets and delivery techniques. Engineering extracellular vesicles (EVs) as an upgraded version of natural EVs holds great potential in regenerative medicine. In this study, we found that the expression of the critical antioxidant and detoxification gene Gstm2 was significantly reduced in aging skin. Thus, we constructed the skin primary fibroblasts-derived EVs encapsulating Gstm2 mRNA (EVs ^Gstm2 ), and found that EVs ^Gstm2 could significantly improve skin homeostasis and accelerate wound healing in aged mice. Mechanistically, we found that EVs ^Gstm2 alleviated oxidative stress damage of aging dermal fibroblasts by modulating mitochondrial oxidative phosphorylation, and promoted dermal fibroblasts to regulate skin epidermal cell function by paracrine secretion of Nascent Polypeptide-Associated Complex Alpha subunit (NACA). Furthermore, we confirmed that NACA is a novel skin epidermal cell protective molecule that regulates skin epidermal cell turnover through the ROS-ERK-ETS-Cyclin D pathway. Our findings demonstrate the feasibility and efficacy of EVs-mediated delivery of Gstm2 for aged skin treatment and unveil novel roles of GSTM2 and NACA for improving aging skin.
(© 2024. The Author(s).)

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82070365 the National Natural Science Foundation of China; JCYJ20190807103407873 the Basic Research General Program of Shenzhen

Keywords: Extracellular vesicles (EVs); Glutathione S-transferase mu 2 (GSTM2); Nascent polypeptide-associated complex alpha subunit (NACA); Needle free injection; Wound healing

EC 2.5.1.18 (Glutathione Transferase)
0 (RNA, Messenger)
EC 2.5.1.18 (glutathione S-transferase Mu 2)

Date Created: 20240602 Date Completed: 20240602 Latest Revision: 20240605

20240605

PMC11145791

10.1186/s12951-024-02541-1

38825668