We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Progranulin released from microglial lysosomes reduces neuronal ferroptosis after cerebral ischemia in mice.
- Authors
Chen, Tingting; Shi, Rubing; Suo, Qian; Wu, Shengju; Liu, Chang; Huang, Shuxian; Haroon, Khan; Liu, Ze; He, Yuyan; Tian, Heng-Li; Wang, Yongting; Tang, Yaohui; Yang, Guo-Yuan; Zhang, Zhijun
- Abstract
The cellular redox state is essential for inhibiting ferroptosis. Progranulin (PGRN) plays an important role in maintaining the cellular redox state after ischemic brain injury. However, the effect of PGRN on ferroptosis and its underlying mechanism after cerebral ischemia remains unclear. This study assesses whether PGRN affects ferroptosis and explores its mechanism of action on ferroptosis after cerebral ischemia. We found endogenous PGRN expression in microglia increased on day 3 after ischemia. In addition, PGRN agonists chloroquine and trehalose upregulated PGRN expression, reduced brain infarct volume, and improved neurobehavioral outcomes after cerebral ischemia compared to controls (p < 0.05). Moreover, PGRN upregulation attenuated ferroptosis by decreasing malondialdehyde and increasing Gpx4, Nrf2, and Slc7a11 expression and glutathione content (p < 0.05). Furthermore, chloroquine induced microglial lysosome PGRN release, which was associated with increased neuron survival. Our results indicate that PGRN derived from microglial lysosomes effectively inhibits ferroptosis during ischemic brain injury, identifying it as a promising target for ischemic stroke therapy.
- Publication
Journal of Cerebral Blood Flow & Metabolism, 2023, Vol 43, Issue 4, p505
- ISSN
0271-678X
- Publication type
Article
- DOI
10.1177/0271678X221145090