Photobiomodulation Drives MiR-136-5p Expression to Promote Injury Repair after Myocardial Infarction

Abstract

Photobiomodulation (PBM) has emerged as an alternative therapy involved in modulating a variety of biological effects. In this study, we verified whether PBM can affect cardiac physiological activity in mice through noninvasive irradiation using light-emitting diodes at a wavelength of 630 nm (LED-Red). We found that the PBM involved in regulating the repair of injured myocardium is wavelength-limited. LED-Red caused cardiomyocytes (CMs) that had exited the cell cycle to divide and proliferate again, and the cell proliferation ratio increased significantly with the accumulation of intracellular photopower. In addition, LED-Red promoted myocardial revascularization and myocardial regeneration, reduced the area of fibrosis in mice with myocardial infarction (MI), and thus improved cardiac contractile function. In regard to the mechanism, miRNA sequencing analysis showed that low-power LED-Red irradiation could induce differential changes in miRNAs in CMs. Among them, miR-136-5p was identified as a cardiac photo-sensitive miRNA and was obviously inhibited after stimulation, which produced a proliferation-promoting effect on CMs. Subsequent luciferase reporter assays confirmed the involvement of Ino80 as a binding target of miR-136-5p in the regulatory process of CM proliferation. Similarly, LED-Red irradiation elevated intracellular Ino80 expression. After knockdown of Ino80, the proliferation-promoting effect of LED-Red on CMs was inhibited. Collectively, this study demonstrates that LED-Red can promote CM proliferation by inhibiting cardiac photo-sensitive miRNA- miR-136-5p expression through targeting Ino80. The findings provided a new potential strategy for the treatment of ischemic cardiomyopathy (ICD).

Light Emitting Diodes Irradiation Regulates miRNA-877-3p to Promote Cardiomyocyte Proliferation

“…Although previous studies have demonstrated the ability of PBM to prolong the growth cycle of outer root sheath cells and neural stem cells in vitro , the effect of LED-Red on CMs proliferation has not been elucidated yet 25 , 26 . In a previous study, we found that LED-Red with a power density of 2.5 mW/cm 2 irradiated for 10 min, could effectively elevating the viability of CMs without phototoxicity on CMs 27 . In addition to this, we determined the effect of LED-Red irradiation on the proliferation of neonatal CMs again.…”

“…LED-Red was identified to significantly increase the viability of CMs compared to blue, green and yellow light. Therefore, red light was chosen as the main light source for PBM 27 . MiRNAs have been reported to play a critical role in regulating key aspects of cardiac physiological and pathological signaling, including the regulation of cardiac regeneration in vitro and in vivo 40 .…”

miR-96-5p regulates myocardial infarction-induced cardiac fibrosis via Smad7/Smad3 pathway

“…The other miRNAs listed in with higher fold change than miR-96-5p, such as miR-382-5p, miR-411-5p, miR-370-3p, and miR-31-5p, as well as their relationships with fibrosis in any other organ have never been studied. miR-199a-5p and miR-136-5p were shown to promote cardiac fibrosis [ 33 , 34 ] , while miR-455-3p was proven to inhibit the process of myocardial fibrosis [35] . Thus, the role of miR-96-5p in cardiac fibrosis was assessed in this study.…”

Exploring the Potential of Energy-Based Therapeutics (Photobiomodulation/Low-Level Laser Light Therapy) in Cardiovascular Disorders: A Review and Perspective

“…Gao et al [ 37 ] determined that LED-Red promoted cardiomyocyte (CM) division and proliferation, myocardial revascularization, and regeneration while reducing fibrosis area in MI mice, improving cardiac contractile function. MiR-136-5p was identified as a cardiac photo-sensitive miRNA with proliferation-promoting effects, and INO80 as a miR-136-5p binding target in CM proliferation regulation [ 37 ]. Grandinetti et al [ 38 ] showed that carvedilol and PBMT comparably ameliorated pulmonary congestion, left ventricle (LV) end-diastolic pressure, LV dilation, and LV systolic function.…”