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.