Identification of CSPG4 as a Biomarker and Therapeutic Target for Infantile Post-Hemorrhagic Hydrocephalus via
Juncao Chen1, Lin Wang2,3, Xiangwen Peng4
1Department of Neonatology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China.
Insights
Researchers identified chondroitin sulfate proteoglycan 4 (CSPG4) as a biomarker for post-hemorrhagic hydrocephalus (PHH) in preterm infants. Targeting CSPG4 may offer a new therapeutic strategy for preventing and treating this serious condition.
Area of Science:
- Neonatal neurology
- Biochemistry
- Proteomics
- Metabolomics
Background:
- Intraventricular hemorrhage (IVH) in preterm neonates is a significant global health issue.
- Post-hemorrhagic hydrocephalus (PHH) is a common and severe complication of IVH.
- Effective diagnostic markers and therapeutic targets for PHH remain critical challenges.
Purpose of the Study:
- To investigate the molecular mechanisms underlying PHH development and recovery.
- To identify novel biomarkers and potential therapeutic targets for PHH.
Main Methods:
- Multi-omics analysis (biochemical, proteomic, metabolomic) of cerebrospinal fluid (CSF) from human cohorts.
- Bioinformatic analysis to identify key pathways and biomarkers.
- In vitro cellular experiments and rat models of PHH.
Main Results:
- Integrative multi-omics analysis revealed dysregulation of ferroptosis, calcium signaling, and cell adhesion pathways in PHH.
- Chondroitin sulfate proteoglycan 4 (CSPG4) was identified as a CSF biomarker, correlating with ventricular size and periventricular leukomalacia.
- CSPG4 silencing in PHH models reduced ferroptosis, cell adhesion, and intracellular calcium (Ca2+) flow.
Conclusions:
- The study elucidates the pathophysiological mechanisms of PHH, highlighting the roles of ferroptosis, calcium, and cell adhesion.
- CSPG4 emerges as a promising diagnostic biomarker and a potential therapeutic target for PHH.
- Targeting CSPG4 may offer a novel strategy for managing PHH in preterm neonates.
Abstract:
Intraventricular hemorrhage in preterm neonates has become a major global health problem and is associated with a high risk of post-hemorrhagic hydrocephalus (PHH). Identifying diagnostic markers and therapeutic targets is a focal challenge in the PHH prevention and control. Here, this study applies multi-omics analyses to characterize the biochemical, proteomic, and metabolomic profiles of the cerebrospinal fluid (CSF) in clinical human cohorts to investigate disease development and recovery processes occurring due to PHH. Integrative multiomics analysis suggests that the over-representation of ferroptosis, calcium, calcium ion binding, and cell adhesion signaling pathways is associated with PHH. Bioinformatic analysis indicates that chondroitin sulfate proteoglycan 4 (CSPG4) is discovered as a CSF biomarker and positively correlated with the ventricular size and the rate of periventricular leukomalacia. Next, it is further demonstrated that these signaling pathways are dysregulated in the choroid plexus (ChP) in PHH by using in vitro cellular experiments and rat models of PHH, whereas CSPG4 silencing can suppress ferroptosis, cell adhesion function, and the intracellular flow of Ca2+. These findings broaden the understanding of the pathophysiological mechanisms of PHH and suggest that CSPG4 may be an effective therapeutic target for PHH.
