miR-203 protects microglia mediated brain injury by regulating inflammatory responses via feedback to MyD88 in ischemia

• miR-203 negatively regulates ischemia induced microglia activation by targeting MyD88.
• Enforced expression of miR-203 inhibits downstream NF-κβ signaling.
• miR-203 represents a novel target regulating neuroinflammation and brain injury.

Much evidence demonstrates that microglia mediated inflammatory responses play an important role in brain injury in ischemia. miRNA is the important factor in regulation of inflammation. However, the effect of miRNA in microglia mediated inflammatory responses has not been well studied. In the study, we demonstrate that miR-203 negatively regulates ischemia induced microglia activation by targeting MyD88, an important adapter protein involved in most Toll-like receptors (TLRs) and interleukin-1 receptor (IL-1R) pathways. Through negative feedback, enforced expression of miR-203 or MyD88 siRNA silencing inhibits downstream NF-κβ signaling and microglia activation, thereby alleviating neuronal injury. These findings reveal that miR-203 represents a novel target regulating neuroinflammation and brain injury, thus offering a new therapeutical strategy for cerebral hypoxic diseases.