Molecular mechanisms of cell proliferation induced by low power laser irradiation

Cell proliferation is a very important physiological effect for low power laser irradiation (LPLI) used in clinical practice. Increased proliferation after LPLI has been shown in many cell types in vitro, including fibroblasts from different systems [1-8], keratinocytes [9], human osteoblasts [10], calvaria osteoblast-like cells [11], lymphocytes [12], mesenchymal stem cells (MSCs) and cardiac stem cells (CSCs) [13], rat Schwann cells [14], aortic smooth muscle cell (SMC) [15], endothelial cells from veins [16] and arteries [17,18], quiescent satellite cells[19,20], human lung adenocarcinoma cells (ASTC-a-1) [21] and HeLa cells [22]. However, the mechanisms of cell proliferation induced by LPLI are poorly understood.Various mechanisms for the mitogenic effects of low power laser irradiation have been proposed, including ligand-free dimerization and activation of specific receptors that are in the "right energetic state" to accept the laser energy, leading to their autophosphorylation and downstream effects [23], activation of calcium channels resulting in increased intracellular calcium concentration and cell proliferation [24-30]. Red to near infrared light is thought to be absorbed by mitochondrial respiratory chain components, resulting in the increase of reactive oxygen species (ROS), and adenosine triphosphate (ATP)/or cyclic AMP, and initiating a signaling cascade which promotes cellular proliferation and cytoprotection [9,12,23,24,31-37]. Following increased ATP and protein synthesis after LPLI, the expressions of growth factors and cytokines increase and ultimately lead to cell proliferation [38,39]. Studies have also shown that light irradiation can alter cellular homeostasis parameters, such as pHi, the redox state of the cell, and expression of redox-sensitive factors like NF-κB, which can lead to a proliferation increase [23,40-42].Recently, a large number of signaling proteins reported play an important key role in the process of LPLI-induced cell proli