Antifibrotic activity of Hypocrellin A united LED red light irradiation on Keloid Fibroblasts through counteracting TGF-β/Smad/autophagy/apoptosis signaling pathway

Keloid disease is characterized by abnormal proliferation of fibroblast and continuous deposition of extracellular matrix (ECM) components. More and more attention in dermopathic is paid to photodynamic therapy (PDT) with visible light. The natural photosensitizer Hypocrellin A (HA) is identified to develop a splendid light induced anticancer, antimicrobial and antiviral activity. In this experiment, we investigated the impacts of HA united light-emitting diode (LED) red light irradiation on human keloid fibroblast cells (KFs). Our results showed that HA united red light irradiation treatment (HA-R-PDT) decreased KFs viability, reduced KFs collagen production and ECM accumulation, inhibited cell proliferation, suppressed cell invasion and induced cell apoptosis. Moreover, our observations demonstrated that TGF-β/Smad signaling pathway and autophagy were restrained by HA-R-PDT. TGF-β1 could accommodate autophagy in KFs through both Smad and ERK pathway, while inhibiting autophagy could mediate TGF-β1 level by the negative feedback. Therefore, HA-R-PDT could suppress cell hyper-proliferation, collagen synthesis and ECM accumulation in KFs via regulating TGF-β1-ERK-autophagy-apoptosis signaling pathway. HA-R-PDT deserves systematic investigation as a potential therapeutic strategy for keloid treatment and autophagy might be a promising candidate in the therapy of KFs.