Cellular and molecular mechanisms of tissue repair by fascia

Ye, Haifeng (2023): Cellular and molecular mechanisms of tissue repair by fascia. Dissertation, LMU München: Medizinische Fakultät

Abstract

Aging is an important factor affecting wound healing in the skin. Former research demonstrated that wound healing progresses slowly and is delayed in aging skin compared to adolescent skin. Aged and injured skin also tends to develop into chronic wounds, and that removing senescent cells from the skin can accelerate wound healing(Wilkinson and Hardman, 2020; Yousefzadeh et al., 2018). However, it has also been shown that senescent cells in the skin contribute to wound healing, ultimately leading to the formation of smaller scars. Therefore, it is unclear what the exact mechanism of aging is in affecting wound healing. In this study, we explored the differences and mechanisms between young and aged skin wounds using in vitro skin culture techniques, in vivo skin wound models, skin chimeric grafting experiments, in vitro cell transplantation experiments, real-time imaging techniques, three-dimensional imaging techniques, immunofluorescence staining and histological staining. The cumulative data indicates that the differences in wound healing dynamics between aged and young skin are due to the heterogeneity of fascia fibroblasts. Specifically, the differentiation capacity of fascia fibroblasts is greatly reduced in aging skin, leading to a decrease in fascia contractility and transport into wounds, which ultimately leads to slow skin wound closure and delayed wound healing. The use of a Wnt Signaling agonist (CHIR) can reactivate the differentiation capacity of aged fibroblasts, increasing the contractility capacity of aged fascia, accelerating the closure of aged wounds, and promoting wound healing. These finding explains how wound healing is slowed down during aging, revealing Wnt signaling can activate or reprogram aged fascial fibroblasts to promote wound healing, and provides a new basic research and translational perspectives to accelerate and improve wound healing of aged skin.

• 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: 11. April 2023
• 1. Bericht­erstatter:in: Behr, Jürgen