AAV-mediated gene delivery in the cutaneous wound healing

Zhu, Shaohua (2023): AAV-mediated gene delivery in the cutaneous wound healing. Dissertation, LMU München: Medizinische Fakultät

Abstract

Cutaneous wound healing is a complex physiological process. Abnormal skin damage repair such as chronic wounds caused by diabetes, or excessive scar formation places a huge burden on the patient and society. AAV is widely used in biological research and is an ideal tool for human gene therapy. But AAV is rarely used in the research of cutaneous wound repair due to several technical issues. Here, we identified that sodium butyrate, a histone deacetylase, can greatly enhance the viral transduction of AAV6 serotypes in the wound healing model – SCAD (scar in a dish). We also optimized the transgenic plasmid using 2A self-cleavage peptide instead of the flexible linker, achieving robust co-expression of GFP and our target gene. Using the optimized system, we investigated the function of Akr1c18 in cutaneous wound healing. Akr1c18 is a steroid dehydrogenase and is mainly involved in the progesterone signal pathway. We found that Akr1c18 overexpression could slightly affect the fibroblast migration in the SCAD model and Akr1c18 overexpressed fibroblast have longer cell shape. However, the overall effect of Akr1c18 overexpression in wound healing is limited. Single-cell RNA analysis showed some elevated levels of progesterone response genes in mature wound fibroblast having reduced Akr1c18 expression. Based on the function of Akr1c18 as a progesterone inactivator, reduced expression of Akr1c18 in mature wound fibroblasts may lead to elevated progesterone levels in the skin, leading to increased progesterone responsive gene expression in wound fibroblasts.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 2. März 2023
• 1. Bericht­erstatter:in: Rinkevich, Yuval