Fluorescent Light Energy (FLE) Acts on Mitochondrial Physiology Improving Wound Healing.

Letizia Ferroni,Paolo Pinton,Lise Hébert,Michael Nielsen,Franco Bassetto,Simone Patergnani,Shannon E Campbell,Barbara Zavan,Michela Zago,Carlotta Scarpa

doi:10.3390/jcm9020559

Abstract

Fluorescent light energy (FLE) has been used to treat various injured tissues in a non-pharmacological and non-thermal fashion. It was applied to stimulate cell proliferation, accelerate healing in chronic and acute wounds, and reduce pain and inflammation. FLE has been shown to reduce pro-inflammatory cytokines while promoting an environment conducive to healing. A possible mechanism of action of FLE is linked to regulation of mitochondrial homeostasis. This work aims to investigate the effect of FLE on mitochondrial homeostasis in an in vitro model of inflammation. Confocal microscopy and gene expression profiling were performed on cultures of inflamed human dermal fibroblasts treated with either direct light from a multi-LED lamp, or FLE from either an amorphous gel or sheet hydrogel matrix. Assessment using confocal microscopy revealed mitochondrial fragmentation in inflamed cells, likely due to exposure to inflammatory cytokines, however, mitochondrial networks were restored to normal 24-h after treatment with FLE. Moreover, gene expression analysis found that treatment with FLE resulted in upregulation of uncoupling protein 1 (UCP1) and carnitine palmitoyltransferase 1B (CPT1B) genes, which encode proteins favoring mitochondrial ATP production through oxidative phosphorylation and lipid β-oxidation, respectively. These observations demonstrate a beneficial effect of FLE on mitochondrial homeostasis in inflamed cells.

Highlights

Wound healing follows a series of complex overlapping processes that leads to closure of the wound and restoration of the epithelial layer, including hemostasis, inflammation, cell proliferation and tissue remodeling [1].After an injury to skin, the exposed sub-endothelium, collagen and tissue factors activate platelet aggregation to form a clot
Analysis of the mitochondrial morphology was performed in all human dermal fibroblasts (HDFs) conditions: (a) healthy HDFs in normal media (Healthy), (b) inflamed HDFs in TNFα/IL-1β inflammatory cocktail (Inflamed), (c) inflamed HDFs treated with light alone (Light), (d) inflamed HDFs treated with Fluorescent light energy (FLE)-Gel (Gel), and (e) inflamed HDFs treated with FLE-Matrix (Matrix)
When inflamed cells were exposed to either direct light (Light) or FLE (Gel or Matrix) the mitochondrial network showed preliminary signs of improvement at 30-min post-treatment, with some statistical differences already observed in FLE-treated cells

Summary

Introduction

Wound healing follows a series of complex overlapping processes that leads to closure of the wound and restoration of the epithelial layer, including hemostasis, inflammation, cell proliferation and tissue remodeling [1]. After an injury to skin, the exposed sub-endothelium, collagen and tissue factors activate platelet aggregation to form a clot (hemostasis). Macrophages accumulate in the inflammatory phase facilitating phagocytosis of bacteria and damaged tissue. The proliferative phase follows the inflammatory phase, and is characterized by accumulation of fibroblasts and production of connective tissue. Fibroblasts play a critical role in supporting normal wound healing due to their involvement in several key processes, including breakdown of fibrin clot, creation of new ECM and collagen structures, and contraction of the wound [3]. The healing process involves numerous cellular and biosynthetic processes, which all require energy in the form of adenosine triphosphate (ATP), as well as amino acids, and other precursor molecules to replace damaged tissue [4,5,6]

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