Antimicrobial photodynamic therapy with RLP068 kills methicillin-resistantStaphylococcus aureusand improves wound healing in a mouse model of infected skin abrasion PDT with RLP068/Cl in infected mouse skin abrasion

Photodynamic therapy (PDT) is a promising new method to eliminate microbial infection and promote wound healing. Its effectiveness has been confirmed by some studies; however, the mechanisms of PDT in wound healing remain obscure. We used mouse skin wounds infected with Pseudomonas aeruginosa as a research object to explore the therapeutic effects and mechanisms of 5-aminolevulinic acid photodynamic therapy (ALA-PDT). ALA-PDT treatment significantly reduced the load of P. aeruginosa in the wound and surrounding tissues and promoted the healing of skin wounds in mice. Hematoxylin-eosin (HE) and Sirius red staining showed that ALA-PDT promoted granulation tissue formation, angiogenesis, and collagen regeneration and remodeling. After ALA-PDT treatment, the expression of inflammatory factors (TNF-α and IL-1β) first increased and then decreased, while the secretion of growth factors (TGF-β-1 and VEGF) increased gradually after treatment. Furthermore, ALA-PDT affected the polarization state of macrophages, activating and promoting macrophages from an M1 to an M2 phenotype. In conclusion, ALA-PDT can not only kill bacteria but also promote wound healing by regulating inflammatory factors, collagen remodeling and macrophages. This study further clarifies the mechanism of PDT in the healing of infectious skin wounds and provides further experimental evidence for its clinical treatment of skin wounds infected by P. aeruginosa.

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PC4 serves as a negative regulator of skin wound healing in mice

Burns & Trauma ◽

10.1093/burnst/tkaa010 ◽

2020 ◽

Vol 8 ◽

Cited By ~ 1

Author(s):

Fengying Liao ◽

Long Chen ◽

Peng Luo ◽

Zhongyong Jiang ◽

Zelin Chen ◽

...

Keyword(s):

Wound Healing ◽

Mouse Model ◽

Mouse Skin ◽

Skin Wound ◽

Dermal Fibroblasts ◽

Negative Regulator ◽

Collagen Deposition ◽

Skin Wound Healing ◽

Primary Fibroblasts

Abstract Background Human positive cofactor 4 (PC4) was initially characterized as a multifunctional transcriptional cofactor, but its role in skin wound healing is still unclear. The purpose of this study was to explore the role of PC4 in skin wound healing through PC4 knock-in mouse model. Methods A PC4 knock-in mouse model (PC4+/+) with a dorsal full-thickness wound was used to investigate the biological functions of PC4 in skin wound healing. Quantitative PCR, Western blot analysis and immunohistochemistry were performed to evaluate the expression of PC4; Sirius red staining and immunofluorescence were performed to explore the change of collagen deposition and angiogenesis. Proliferation and apoptosis were detected using Ki67 staining and TUNEL assay. Primary dermal fibroblasts were isolated from mouse skin to perform cell scratch experiments, cck-8 assay and colony formation assay. Results The PC4+/+ mice were fertile and did not display overt abnormalities but showed an obvious delay in cutaneous healing of dorsal skin. Histological staining showed insufficient re-epithelialization, decreased angiogenesis and collagen deposition, increased apoptosis and decreased cell proliferation in PC4+/+ skin. Our data also showed decreased migration rate and proliferation ability in cultured primary fibroblasts from PC4+/+ mice in vitro. Conclusions This study suggests that PC4 might serve as a negative regulator of skin wound healing in mice.

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