Radiation Induces Pericyte-Myofibroblast Transition

Area of Science:

• Oncology
• Cell Biology
• Radiotherapy Research

Background:

• Radiation therapy is a cornerstone of cancer treatment, acting through direct DNA damage and indirect vascular effects.
• The precise impact of radiation on tumor pericytes, crucial for vascular stability, remains largely uncharacterized.
• Understanding radiation's effects on pericytes is vital for optimizing therapeutic strategies.

Purpose of the Study:

• To investigate the effects of radiation on pericyte differentiation and maturation.
• To elucidate the underlying molecular mechanisms by which radiation influences pericytes.
• To determine if radiation induces pericyte-to-myofibroblast transition in vitro and in vivo.

Main Methods:

• Irradiation of mouse embryonic mesenchymal pericyte precursor cells (10T1/2) and human placental pericytes (hPC-PL).
• Assessment of pericyte differentiation, maturation, and myofibroblast transition using flow cytometry, qRT-PCR, and immunofluorescence.
• Analysis of signaling pathways (Akt, ROS) and in vivo tumor models (MC38 in NG2DsRed mice) to confirm radiation-induced pericyte-myofibroblast transition.

Main Results:

• Radiation promoted pericyte differentiation and increased myofibroblast marker expression in vitro.
• Radiation activates the Akt signaling pathway, and its inhibition, along with ROS inhibition, suppressed radiation-induced myofibroblast marker expression.
• In vivo studies confirmed radiation-induced pericyte-to-myofibroblast transition in tumors, with Akt inhibition reducing vimentin expression.

Conclusions:

• Radiation exposure promotes pericyte maturation and their transition into myofibroblasts.
• The Akt signaling pathway plays a critical role in mediating radiation's effects on pericytes.
• These findings provide insights into radiation-induced vascular changes and potential therapeutic targets.