Photobiomodulation Therapy for Thrombocytopenia by Upregulating Thrombopoietin Expression via the ROS‐dependent Src/ERK/STAT3 Signaling Pathway

BACKGROUND Chemotherapy-induced thrombocytopenia (CIT) can increase the risk of bleeding, which may delay or prevent the administration of anticancer treatment schedules. Photobiomodulation therapy (PBMT), a non-invasive physical treatment, has been proposed to improve thrombocytopenia; however, its underlying regulatory mechanism is not fully understood. OBJECTIVE To further investigate the mechanism of thrombopoietin (TPO) in megakaryocytopoiesis and thrombopoiesis. METHODS Multiple approaches such as western blotting, cell transfection, flow cytometry and animal studies were utilized to explore the effect and mechanism of PBMT on thrombopoiesis. RESULTS PBMT prevented a severe drop in platelet count by increasing platelet production, and then ameliorated CIT. Mechanistically, PBMT significantly upregulated hepatic TPO expression in a thrombocytopenic mouse model, which promoted megakaryocytopoiesis and thrombopoiesis. The levels of TPO mRNA and protein increased by PBMT via the Src/ERK/STAT3 signaling pathway in hepatic cells. Furthermore, the generation of the reactive oxygen species was responsible for PBMT-induced activation of Src and its downstream target effects. CONCLUSIONS Our research suggests that PBMT is a promising therapeutic strategy for the treatment of CIT.