Int J Biol Sci 2022; 18(7):2980-2993. doi:10.7150/ijbs.71440 This issue
1. Department of Laboratory Medicine at the Fourth Affiliated Hospital, and Department of Pharmacy at the Second Affiliated Hospital, Harbin Medical University, Harbin, China
2. Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education) at College of Pharmacy, Harbin Medical University, Harbin, China
3. Northern Translational Medicine Research and Cooperation Center, Heilongjiang Academy of Medical Sciences, Harbin Medical University, Harbin, ChinaHarbin, China
4. Institute of Clinical Pharmacy, the Heilongjiang Key Laboratory of Drug Research, Harbin Medical University, Harbin, China
# These authors contributed equally to this work.
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).
Keywords: Photobiomodulation therapy, Light-emitting diodes, Cardiomyocyte proliferation, Myocardial regeneration, Myocardial infarction.