ErbB4 protects against neuronal apoptosis via activation of YAP/PIK3CB signaling pathway in a rat model of subarachnoid hemorrhage

Feng Yan, Xiaoxiao Tan, Weifeng Wan, Brandon J. Dixon, Ruiming Fan, Budbazar Enkhjargal, Qian Li, Jianmin Zhang, Gao Chen, John H. Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

Neuronal apoptosis is a central pathological process in subarachnoid hemorrhage (SAH)-induced early brain injury. Previous studies indicated that ErbB4 (EGFR family member v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4) is essential for normal development and maintenance of the nervous system. In this study, we explored the neuroprotective effects of ErbB4 and its downstream YAP (yes-associated protein)/PIK3CB signaling pathway in early brain injury after SAH in a rat model using the endovascular perforation method. Rats were neurologically evaluated with the Modified Garcia Scale and beam balance test at 24 h and 72 h after SAH. An ErbB4 activator Neuregulin 1β1 (Nrg 1β1), ErbB4 siRNA and YAP siRNA were used to explore this pathway. The expression of p-ErbB4 and YAP was significantly increased after SAH. Multiple immunofluorescence labeling experiments demonstrated that ErbB4 is mainly expressed in neurons. Activation of ErbB4 and its downstream signals improved the neurological deficits after SAH and significantly reduced neuronal cell death. Inhibition of ErbB4 reduced YAP and PIK3CB expression, and aggravated cell apoptosis. YAP knockdown reduced the PIK3CB level and eliminated the anti-apoptotic effects of ErbB4 activation. These findings indicated that ErbB4 plays a neuroprotective role in early brain injury after SAH, possibly via the YAP/PIK3CB signaling pathway.

Original languageEnglish
Pages (from-to)92-100
Number of pages9
JournalExperimental Neurology
Volume297
DOIs
StatePublished - Nov 2017

ASJC Scopus Subject Areas

  • Neurology
  • Developmental Neuroscience

Keywords

  • Apoptosis
  • Early brain injury
  • ErbB4
  • PIK3CB
  • Subarachnoid hemorrhage
  • YAP
  • Phosphatidylinositol 3-Kinases/metabolism
  • Rats
  • Male
  • Receptor, ErbB-4/biosynthesis
  • Random Allocation
  • YAP-Signaling Proteins
  • Rats, Sprague-Dawley
  • Subarachnoid Hemorrhage/metabolism
  • Signal Transduction/physiology
  • Dose-Response Relationship, Drug
  • Animals
  • Apoptosis/physiology
  • Neurons/metabolism
  • Apoptosis Regulatory Proteins/metabolism
  • Neuroprotective Agents/metabolism
  • Disease Models, Animal

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