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-beta 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)-beta 1 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-beta 1.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.

Automated summary

The review discusses the central role of the TGF-beta pathway in various physiological processes and the challenges faced in developing targeted therapeutics. The use of photobiomodulation (PBM) treatments for selectively activating endogenous latent TGF-beta 1 offers a novel therapeutic approach with growing evidence for its potential roles in cancer immunotherapy and stem cell biology.