Scholarlink

<p>Spinal cord ischemia–reperfusion injury (SCI/RI) triggers severe mitochondrial dysfunction and neuronal death. While mitochondrial transplantation (MT) is a promising strategy, its therapeutic potency remains limited. This study identifies the transcription factor Engrailed-1 (En-1) as a key regulator of mitochondrial homeostasis and a potential enhancer of MT. En-1 expression is significantly downregulated in SCI/RI models, whereas its restoration via hypoxic preconditioning or overexpression markedly improves neuronal survival. Mechanistically, En-1 stabilizes mitochondrial membrane potential, attenuates reactive oxygen species (ROS) production, and inhibits apoptosis by transcriptionally upregulating PDGFC. Mitochondria harvested from En-1-overexpressing cells (OE-En1-Mito) exhibit superior bioenergetic profiles and rapid neuronal uptake compared to unmodified mitochondria. In vitro, OE-En1-Mito increased ATP production and antioxidant activity; in vivo, transplantation preserved neuronal integrity and improved motor recovery in SCI/RI rats. Notably, silencing PDGFC in donor mitochondria abolished these neuroprotective benefits. Thus, En-1-modified MT provides superior neuroprotection for SCI/RI by leveraging the En-1/PDGFC axis.</p><p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Engrailed-1 potentiates mitochondrial transplant neuroprotection in spinal cord ischemia-reperfusion injury

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月7日

查看全文
  • Wei Wang,
  • Rui Tang,
  • Shilun Gao,
  • Xiaotian Han,
  • Teng Shi,
  • Tianxiang Gu,
  • Enyi Shi

摘要

Spinal cord ischemia–reperfusion injury (SCI/RI) triggers severe mitochondrial dysfunction and neuronal death. While mitochondrial transplantation (MT) is a promising strategy, its therapeutic potency remains limited. This study identifies the transcription factor Engrailed-1 (En-1) as a key regulator of mitochondrial homeostasis and a potential enhancer of MT. En-1 expression is significantly downregulated in SCI/RI models, whereas its restoration via hypoxic preconditioning or overexpression markedly improves neuronal survival. Mechanistically, En-1 stabilizes mitochondrial membrane potential, attenuates reactive oxygen species (ROS) production, and inhibits apoptosis by transcriptionally upregulating PDGFC. Mitochondria harvested from En-1-overexpressing cells (OE-En1-Mito) exhibit superior bioenergetic profiles and rapid neuronal uptake compared to unmodified mitochondria. In vitro, OE-En1-Mito increased ATP production and antioxidant activity; in vivo, transplantation preserved neuronal integrity and improved motor recovery in SCI/RI rats. Notably, silencing PDGFC in donor mitochondria abolished these neuroprotective benefits. Thus, En-1-modified MT provides superior neuroprotection for SCI/RI by leveraging the En-1/PDGFC axis.