RGD Reference Report - ErbB4 protects against neuronal apoptosis via activation of YAP/PIK3CB signaling pathway in a rat model of subarachnoid hemorrhage. - Rat Genome Database

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

Authors: Yan, Feng  Tan, Xiaoxiao  Wan, Weifeng  Dixon, Brandon J  Fan, Ruiming  Enkhjargal, Budbazar  Li, Qian  Zhang, Jianmin  Chen, Gao  Zhang, John H 
Citation: Yan F, etal., Exp Neurol. 2017 Nov;297:92-100. doi: 10.1016/j.expneurol.2017.07.014. Epub 2017 Jul 27.
RGD ID: 151893490
Pubmed: PMID:28756200   (View Abstract at PubMed)
DOI: DOI:10.1016/j.expneurol.2017.07.014   (Journal Full-text)

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 24h and 72h 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Erbb4  (erb-b2 receptor tyrosine kinase 4)
Nrg1  (neuregulin 1)
Pik3cb  (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta)
Yap1  (Yes1 associated transcriptional regulator)

Genes (Mus musculus)
Erbb4  (erb-b2 receptor tyrosine kinase 4)
Nrg1  (neuregulin 1)
Pik3cb  (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta)
Yap1  (yes-associated protein 1)

Genes (Homo sapiens)
ERBB4  (erb-b2 receptor tyrosine kinase 4)
NRG1  (neuregulin 1)
PIK3CB  (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta)
YAP1  (Yes1 associated transcriptional regulator)


Additional Information