Photobiomodulation-Activated Latent Transforming Growth Factor-β1: A Critical Clinical Therapeutic Pathway and an Endogenous Optogenetic Tool for Discovery

Objective: The central role of the TGF-β pathway in embryonic development, immune responses, tissue healing, and malignancies is well established. Prior attempts with small molecules, peptides, and regulatory RNAs have failed mainly due to off-target effects in clinical studies. This review outlines the evidence for selectively activating the endogenous, latent transforming growth factor (TGF)-β1 with photobiomodulation (PBM) treatments. Background: Light treatments play a central role in current-directed energy therapeutics in medicine. Therapeutic use of low-dose light treatments has been noted since the 1960s. However, the breadth of treatments and inconsistencies with clinical outcomes have led to much skepticism. This can be primarily attributed to a lack of understanding of the fundamental light-tissue interactions and optimization of clinical treatment protocols. Methods: Recent advances in molecular mechanisms and improved biophotonic device technologies have led to a resurgence of interest in this field. Results: Over the past two decades, our work has focused on outlining a direct molecular mechanism involving PBM-generated redox-mediated activation of endogenous latent TGF-β1. Conclusions: Despite its critical roles in these processes, the complexity and cross talk in this potent growth factor signaling network have prevented the development of directed targeted therapeutics. PBM treatments offer a novel therapeutic and discovery tool in this aspect, especially with the growing evidence for its roles in cancer immunotherapy and stem cell biology.