Activin A rescues preterm brain injury through a novel Noggin/BMP4/Id2 signaling pathway

Su,Xiaojuan; Ying,Junjie; Xiao,Dongqiong; Qiu,Xia; Li,Shiping; Zhao,Fengyan; Tang,Jun

doi:10.3892/ijmm.2022.5215

Activin A rescues preterm brain injury through a novel Noggin/BMP4/Id2 signaling pathway

Authors:
- Xiaojuan Su
- Junjie Ying
- Dongqiong Xiao
- Xia Qiu
- Shiping Li
- Fengyan Zhao
- Jun Tang
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Affiliations: Department of Pediatrics/Key Laboratory of Birth Defects and Related Diseases of Women and Children (Ministry of Education), West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
Published online on: December 14, 2022 https://doi.org/10.3892/ijmm.2022.5215
Article Number: 12
Copyright: © Su et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Activin A (Act A) has been reported to promote oligodendrocyte progenitor cell (OPC) differentiation in vitro and improve neurological outcomes in adult mice. However, the roles and mechanisms of action of Act A in preterm brain injury are unknown. In the present study, P5 rats were subjected to hypoxia‑ischemia to establish a neonatal white matter injury (WMI) model and Act A was injected via the lateral ventricle. Pathological characteristics, OPC differentiation, myelination, and neurological performance were analyzed. Further, the involvement of the Noggin/BMP4/Id2 signaling pathway in the roles of Act A in WMI was explored. Act A attenuated pathological damage, promoted OPC differentiation, enhanced myelin sheath and myelinated axon formation, and improved neurological performance of WMI rats. Moreover, Act A enhanced noggin expression, which, in turn, inhibited the expression of bone morphogenetic protein 4 (BMP4) and inhibitor of DNA binding 2 (Id2). Furthermore, upregulation of Id2 completely abolished the rescue effects of Act A in WMI rats. In conclusion, the present findings suggested that Act A rescues preterm brain injury via targeting a novel Noggin/BMP4/Id2 signaling pathway.

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