Abstract：
Sonic hedgehog (Shh) is a secreted glycopeptide belonging to the hedgehog family that is essential for morphogenesis during embryonic development. The Shh signal is mediated by two membrane proteins, Patched-1 (Ptch-1) and Smoothened (Smo), following the activation of transcription factors such as Gli. Shh decreases the permeability of the blood-brain barrier (BBB) and plays a key role in its function. In the damaged brain, BBB function is remarkably disrupted. The BBB disruption causes brain edema and neuroinflammation resulting from the extravasation of serum components and the infiltration of inflammatory cells into the cerebral parenchyma. Multiple studies have suggested that astrocyte is a source of Shh and that astrocytic Shh production is increased in the damaged brain. In various experimental animal models of acute brain injury, Shh or Shh signal activators alleviate BBB disruption by increasing tight junction proteins in endothelial cells. Furthermore, activation of astrocytic Shh signaling reduces reactive astrogliosis, neuroinflammation, and increases the production of vascular protective factors, which alleviates BBB disruption in the damaged brain. These findings suggest that astrocytic Shh and Shh signaling protect BBB function in the damaged brain and that target drugs for Shh signaling are expected to be novel therapeutic drugs for acute brain injuries.
摘要：
Sonichedgehog（Shh）是一种分泌的糖肽，属于hedgehog家族，对胚胎发育过程中的形态发生至关重要。Shh信号由两种膜蛋白介导,补丁-1（Ptch-1）和平滑（Smo），在转录因子如Gli的激活之后。Shh降低血脑屏障（BBB）的通透性，并在其功能中起关键作用。在受损的大脑中，BBB功能被显著破坏。BBB破坏引起脑水肿和神经炎症，这是由于血清成分的外渗和炎症细胞浸润到脑实质中所致。多项研究表明，星形胶质细胞是Shh的来源，并且星形胶质细胞Shh的产生在受损的大脑中增加。在各种急性脑损伤的实验动物模型中，Shh或Shh信号激活剂通过增加内皮细胞中的紧密连接蛋白来减轻BBB破坏。此外，星形胶质细胞Shh信号的激活减少了反应性星形胶质细胞增生，神经炎症，并增加血管保护因子的产生，这减轻了受损大脑中的BBB破坏。这些发现表明星形胶质细胞Shh和Shh信号保护受损大脑中的BBB功能，并且Shh信号的靶向药物有望成为急性脑损伤的新型治疗药物。
