Monocyte-derived exosomal periostin driven by histone lactylation contributes to retinal neovascularization

Exosomes are signaling messengers facilitating intercellular communication by delivering molecular cargo. Here, we observed increased levels of exosomal periostin (POSTN) in the blood plasma of patients with proliferative diabetic retinopathy (PDR). Monocytes contributed to elevated levels of exosomal POSTN, and deletion of <i>Postn</i> in myeloid cells reduced retinal neovascularization (RNV). Monocytes isolated from the blood of PDR patients or under high glucose conditions exhibited heightened glycolytic activity and elevated histone lactylation levels, particularly H4K8 lactylation (H4K8la). Knockout of hexokinase 2 (<i>Hk2</i>) in myeloid cells led to reduced H4K8la and POSTN levels and inhibited RNV. Exogenous exosomal POSTN partially reversed the angiogenic defects caused by <i>Postn</i> or <i>Hk2</i> deletion in myeloid cells. Mechanistically, exosomal POSTN stabilized hypoxia-inducible factor -1 alpha and upregulated the expression of angiogenic genes. Notably, treatment with metformin reduced RNV by decreasing monocyte glycolysis and lowering exosomal POSTN levels. In summary, these findings underscore the critical role of circulating exosomal POSTN in RNV and highlight its potential as a therapeutic target for angiogenic retinopathies.

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Publication Details

Journal
Proceedings of the National Academy of Sciences
Published
2025-10-28
DOI
https://doi.org/10.1073/pnas.2501704122
Citations
2
Primary Topic
Extracellular vesicles in disease
Type
article
Field-Weighted Citation Impact
1.61
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article

Monocyte-derived exosomal periostin driven by histone lactylation contributes to retinal neovascularization

Qing Peng, Haorui Zhang, Xi Shen, Min Zhao et al.
2 citations
Proceedings of the National Academy of Sciences
Extracellular vesicles in disease
1.61
article

Monocyte-derived exosomal periostin driven by histone lactylation contributes to retinal neovascularization

Qing Peng, Haorui Zhang, Xi Shen, Min Zhao, Wenbin Zou, Hao Zeng, Yongxuan Liu, Hongyuan Song, Wei Shen, Yukun Zhou, Lin Zhang, Wen Zhou, Zheng Nie, Huimin Zhu, Shikun Wang, Mengzhu Wang, Yuxin Jiang, Guangping Gao, Jiawei Zhao, Liqiang Wang
article en
2 citations

Abstract

Exosomes are signaling messengers facilitating intercellular communication by delivering molecular cargo. Here, we observed increased levels of exosomal periostin (POSTN) in the blood plasma of patients with proliferative diabetic retinopathy (PDR). Monocytes contributed to elevated levels of exosomal POSTN, and deletion of <i>Postn</i> in myeloid cells reduced retinal neovascularization (RNV). Monocytes isolated from the blood of PDR patients or under high glucose conditions exhibited heightened glycolytic activity and elevated histone lactylation levels, particularly H4K8 lactylation (H4K8la). Knockout of hexokinase 2 (<i>Hk2</i>) in myeloid cells led to reduced H4K8la and POSTN levels and inhibited RNV. Exogenous exosomal POSTN partially reversed the angiogenic defects caused by <i>Postn</i> or <i>Hk2</i> deletion in myeloid cells. Mechanistically, exosomal POSTN stabilized hypoxia-inducible factor -1 alpha and upregulated the expression of angiogenic genes. Notably, treatment with metformin reduced RNV by decreasing monocyte glycolysis and lowering exosomal POSTN levels. In summary, these findings underscore the critical role of circulating exosomal POSTN in RNV and highlight its potential as a therapeutic target for angiogenic retinopathies.

Proceedings of the National Academy of SciencesVol. 122(44)
Naval Medical Research Command (US), Second Military Medical University (CN), Shanghai Jiao Tong University (CN), Naval University of Engineering (CN), Ruijin Hospital (CN), Chinese PLA General Hospital (CN), Chinese General Hospital College of Nursing and Liberal Arts (PH), Changhai Hospital (CN), Shanghai First People's Hospital (CN), Xijing Hospital (CN), Air Force Medical University (CN)
Openalex Percentile: Top 14%
Extracellular vesicles in disease
1.61
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