2. Academic Validation
  3. Circular RNA PTPN4 Contributes to Blood-Brain Barrier Disruption during Early Epileptogenesis

Circular RNA PTPN4 Contributes to Blood-Brain Barrier Disruption during Early Epileptogenesis

  • Adv Sci (Weinh). 2025 Dec 14:e02250. doi: 10.1002/advs.202502250.
Jiurong Yang 1,  Yang Hu 1,  Feiyu Wang 1,  Xintao Peng 1 2,  Honggang Qi 1,  Yuanyuan Yao 1,  Canyu Zhang 1,  Lijie Zhou 1,  Xuemei Liang 1,  Kang Xu 1,  Cong Zhang 1,  Aifeng Zhang 3,  Chen Chen 4,  Yu Zeng 5,  Chenchen Zhang 6,  Guangming Gan 6 7,  Xinjian Zhu 1
Affiliations

Affiliations

  • 1 Department of Pharmacology, Medical School of Southeast University, Nanjing, 210009, China.
  • 2 Sanbo Brain Hospital, Capital Medical University, Beijing, 100093, China.
  • 3 Department of Pathology, Medical School of Southeast University, Nanjing, 210009, China.
  • 4 Functional Experimental Center, Medical School of Southeast University, Nanjing, 210009, China.
  • 5 National Residents Clinical Skills Training Center, Medical School of Southeast University, Nanjing, 210009, China.
  • 6 Transmission Electron Microscopy Center, Medical School of Southeast University, Nanjing, 210009, China.
  • 7 Department of Genetics and Developmental Biology, Medical School of Southeast University, Nanjing, 210009, China.
PMID: 41391036 DOI: 10.1002/advs.202502250
Abstract

Circular RNAs (circRNAs) are crucial regulators of gene expression, exhibiting dynamic expression patterns during both normal brain development and diverse pathological states. This study reports the elevated expression of CircPTPN4 in the brain tissue and plasma during early epileptogenesis in a murine temporal lobe epilepsy model. Overexpression of CircPTPN4 disrupts the tight junctions of brain microvascular endothelial cells (BMECs), compromising blood-brain barrier (BBB) integrity. Mechanistically, CircPTPN4 functions as a competitive endogenous RNA by sequestering miR-145a-5p, thereby upregulating endothelin-converting enzyme-1 (ECE-1). Subsequent ECE-1-mediated endothelin-1 (ET-1) production activates the p38/MAPK pathway, downregulating tight junction protein expression. Knockdown of CircPTPN4 attenuated tight junction disruption and BBB impairment during acute epileptogenesis while reducing spontaneous seizure frequency in chronic epilepsy. These findings establish the CircPTPN4/miR-145a-5p/ECE-1 axis as both a diagnostic biomarker and therapeutic target for BBB preservation in early-stage epilepsy.

Keywords

blood‐brain barrier; circPTPN4; endothelin converting enzyme‐1; epilepsy; miR‐145.

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