2. Academic Validation
  3. Exosomes from polarized Microglia: Proteomic insights into potential mechanisms affecting intracerebral hemorrhage

Exosomes from polarized Microglia: Proteomic insights into potential mechanisms affecting intracerebral hemorrhage

  • Gene. 2025 Jan 30:935:149080. doi: 10.1016/j.gene.2024.149080.
Yinan Zhou 1,  Ying Zhang 2,  Dongchen Xu 1,  Chenguang Yang 1,  Xiao Lin 1,  Kunlin Jin 3,  Lei Xia 1,  Qichuan Zhuge 4,  Su Yang 5
Affiliations

Affiliations

  • 1 Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
  • 2 Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Zhejiang-US Joint Laboratory for Aging and Neurological Disease Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
  • 3 Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
  • 4 Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Zhejiang-US Joint Laboratory for Aging and Neurological Disease Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. Electronic address: qc.zhuge@wmu.edu.cn.
  • 5 Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Zhejiang-US Joint Laboratory for Aging and Neurological Disease Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. Electronic address: yangsu@wmu.edu.cn.
PMID: 39510328 DOI: 10.1016/j.gene.2024.149080
Abstract

Intracerebral hemorrhage (ICH) is a devastating form of stroke associated with significant morbidity and mortality. Microglia are intracranial innate immune cell that play critical roles in Intracerebral hemorrhage through direct or indirect means. Vesicle transport is a fundamental mechanism of intercellular communication. Recent studies have identified microglia in specific polarized states correlate with pathogenesis, material and signal transmission in ICH through derived extracellular vesicles. Diverse polarization states trigger distinct functions, however, the exosome proteomes across these states remain poorly characterized. Here, we hypothesized that microglia exosomal profiles vary with polarization states, impacting their functional repertoire and influencing outcomes in cerebral hemorrhage. In vitro model of cerebral hemorrhage, administration of 20 μg/ml LPS-induced M1 microglia derived exosomes (M1-Exo) with HT22 enhanced hemin-induced neuronal death, while IL-4-induced M2 microglia derived exosomes (M2-Exo) significantly reduced hemin-induced cell Apoptosis and inflammation. Then we identified novel state-specific proteomic profiles of microglia-derived exosomes under these polarization conditions through label-free quantitative mass spectrometry (LFQ-MS). Analysis of protein content identified several exosomal signature proteins and hundreds of differentially expressed proteins across polarization states. Specifically, proteins including UMOD, NLRP3, ACOD1, IL1RN, heme oxygenase 1 (HMOX1), CCL4, and TNFRSF1B in M1-Exo were enriched in inflammatory pathways, while those in M2-Exo exhibited enrichment in Autophagy, ubiquitination, and mitochondrial respiration. The analysis of those diverse exosomal proteins suggested unique proteomic profiles and possible intracellular signal transmission and regulation mechanisms. Together, these findings offer new insights and resources for studying microglia-derived exosome and pave the way for the development of novel therapeutic strategies targeting microglial exosome-mediated pathways.

Keywords

Extracellular vesicles; Intracerebral Hemorrhage; Mass spectrometry; Microglia; Proteomic profile.

Figures
Products