Antifibrotic effects of Hypocrellin A combined with LED red light irradiation on keloid fibroblasts by counteracting the TGF-β/Smad/autophagy/apoptosis signalling pathway

• Published in: Photodiagnosis and photodynamic therapy 2021-06, Vol.34, p.102202-102202, Article 102202
• Main Authors: Niu, Tianhui, Tian, Yan, Shi, Ying, Guo, Guangjin, Tong, Ying, Wang, Guangyun
• Format: Article
• Language: English
• Subjects: Autophagy; Hypocrellin A (HA); Keloid fibroblasts (KFs); Light-emitting diode (LED); Photodynamic therapy (PDT); TGF-β/Smad signalling pathway
• ISSN: 1572-1000; 1873-1597
• DOI: 10.1016/j.pdpdt.2021.102202

•HA combined with red light irradiation treatment could suppress KFs hyperproliferation, collagen synthesis and ECM accumulation.•HA-R-PDT could regulate KFs through the TGF-β1-ERK-autophagy-apoptosis signaling pathway TGF-β1 could accommodate autophagy in KFs through both the Smad and ERK pathways.•Autophagy might be a promising candidate in the treatment of KFs. Keloids are characterized by abnormal proliferation of fibroblasts and continuous deposition of extracellular matrix (ECM) components. In the field of dermopathy, photodynamic therapy (PDT) with visible light has been increasingly investigated. The natural photosensitizer Hypocrellin A (HA) was shown to have excellent light induced anticancer, antimicrobial and antiviral activities. 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 combined with red light irradiation treatment (HA-R-PDT) decreased KF viability, reduced KF collagen production and ECM accumulation, inhibited cell proliferation, suppressed cell invasion and induced cell apoptosis. Moreover, our observations demonstrated that the TGF-β/Smad signalling pathway and autophagy were restrained by HA-R-PDT. TGF-β1 could promote autophagy in KFs through both the Smad and ERK pathways, while inhibition of autophagy altered the TGF-β1 levels through negative feedback. Therefore, HA-R-PDT suppressed cell hyperproliferation, collagen synthesis and ECM accumulation of KFs by regulating the TGF-β1-ERK-autophagy-apoptosis signalling pathway. HA-R-PDT deserves systematic investigation as a potential therapeutic strategy for keloids, and autophagy might be a promising candidate in the treatment of KFs.