Hematoporphyrin monomethyl ether sonodynamic therapy (HMME-SDT) mitigates keloid scarring via the PI3K-AKT signaling...

This study investigates the effects and underlying molecular mechanisms of Hematoporphyrin Monomethyl Ether Sonodynamic Therapy (HMME-SDT) on keloid fibroblasts (KFs) in vitro and in vivo, utilizing animal models.

The activation effect of ultrasound on HMME was ascertained using UV-visible light absorption spectroscopy. The influence of HMME-SDT on KFs was assessed in terms of cell proliferation, migration, reactive oxygen species (ROS) generation, mitochondrial membrane potential, and apoptosis. These parameters were evaluated using assays such as the clone formation test, Transwell, flow cytometry, and immunofluorescence. In a nude mouse keloid model, techniques such as immunohistochemical staining were employed to evaluate changes in vascularization, proliferation, apoptosis, and collagen deposition in keloid tissues following HMME-SDT treatment. The potential molecular mechanisms underpinning the effects of HMME-SDT on KFs were identified using RNA sequencing (RNA-Seq) technology, and validated at the mRNA and protein levels through quantitative real-time PCR (qRT-PCR) and Western Blot analysis.

HMME activation was directly correlated with the ultrasound exposure duration and initial HMME concentration. HMME-SDT induced apoptosis in KFs, primarily through increasing ROS production and reducing mitochondrial membrane potential. Furthermore, it also significantly suppressed KFs proliferation and migration. In the nude mouse keloid model, HMME-SDT notably reduced keloid tissue volume, inhibited tissue vascularization, lowered the Type I and III collagen expression in KFs. RNA-Seq and additional in vitro experiments verified that HMME-SDT suppressed KFs through the PI3K-AKT pathway.

HMME-SDT, with its anti-proliferative and anti-fibrotic properties, presents a promising therapeutic strategy for the treatment of keloid.