ABSTRACT
During the process of photoaging in the skin, Succinylated type I collagen has a significant effect on reversing the damage caused by UVB radiation, with the regulation of cellular ferroptosis being one of its important pathophysiological mechanisms. Specifically, Succinylated type I collagen reduces the expression of key cell cycle regulators P16, P21, and P53, as well as the ferroptosis-related factor Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4), induced by UVB radiation in cells and tissues. Meanwhile, it increases the expression of key factors Glutathione Peroxidase 4 (GPX4) and Solute Carrier Family 7 Member 11 (SLC7A11), which inhibit ferroptosis. Additionally, our study also reveals the impact of Succinylated type I collagen on the levels of malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS) in cells and tissues, directly affecting the cells' ability to cope with oxidative stress. This further suggests that Succinylated type I collagen may improve skin photoaging through various pathways, including regulating ferroptosis, antioxidation, promoting collagen synthesis, protecting the skin barrier, reducing pigmentation, and inhibiting inflammatory responses, contributing to maintaining healthy and youthful skin.
ABSTRACT
The process of wound healing includes the inflammatory stage, which plays an important role. Macrophages can promote inflammatory response and also promote angiogenesis, wound contraction and tissue remodeling required for wound healing. It is crucial to promote macrophages to polarize from M1 pro-inflammatory phenotype to M2 anti-inflammatory phenotype at a critical time for the quality of wound healing. Because mesenchymal stem cell-derived exosomes have broad therapeutic prospects in the field of tissue repair and regeneration, in this study, we explored whether trichostatin A pretreated bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (T-Exo) could promote wound healing by binding to biomaterial scaffolds through certain anti-inflammatory effects. In the cell experiment, we established macrophage inflammation model and then treated with T-Exo, and finally detected the expression levels of macrophage polarization proteins CD206, CD86 and TNF-α, iNOS, and Arg-1 by Western Blot and immunofluorescence staining; detected the expression levels of inflammation-related genes TNF-α, iNOS, IL-1ß, IL-10 and anti-inflammatory genes CD206 and Arg-1 by qRT-PCR; explored the promoting ability of T-Exo to promote cell migration and tube formation by cell scratch experiment and angiogenesis experiment. The results showed that T-Exo could promote the polarization of M1 macrophages to M2 macrophages, and promote the migration and angiogenesis of HUVECs. Because TSA pretreatment may bring about changes in the content and function of BMSCs-derived exosomes, proteomic analysis was performed on T-Exo and unpretreated BMSCs-derived exosomes (Exo). The results showed that the differentially expressed proteins in T-Exo were related to some pathways that promote angiogenesis, cell migration, proliferation, and re-epithelialization. Then, exosome/collagen sponge (T-Exo/Col) biological scaffolds were prepared, and the physicochemical properties and biocompatibility of the scaffolds were investigated. Animal skin wound models were established, and the therapeutic effect and anti-inflammatory effect of T-Exo/Col in wound repair were evaluated by small animal in vivo imaging, H&E staining, Masson trichrome staining, immunohistochemical staining, Western Blot, and qRT-PCR. The results showed that T-Exo significantly promoted wound healing by inhibiting inflammation, thereby further promoting angiogenesis and collagen formation in vivo. Moreover, the existence of Col scaffold in T-Exo/Col enabled T-Exo to achieve a certain sustained release effect. Finally, we further explored whether TSA exerts beneficial effects by inhibiting HDAC6 gene of BMSCs, but the results showed that knockdown of HDAC6 gene would cause oxidative stress damage to BMSCs, which means that TSA does not produce these beneficial effects by inhibiting HDAC6 gene. What molecular mechanisms TSA exerts beneficial effects through needs to be further elucidated in the future.