In summary, 1,25-D3 plays a neuroprotective role in stroke by activating VDR and promoting the activation of TGF-β, which in turn up-regulates the TGF-β/Smad2/3 signaling pathway, increases the release of VEGF and thus promotes angiogenesis, suggesting that this signaling pathway may be an effective target for ischemic stroke treatment. The gene discussed is SMAD2; the disease is ischemic stroke.