Biglycan stimulates retinal pathological angiogenesis via up-regulation of CXCL12 expression in pericytes.

IF 4.4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY The FASEB Journal Pub Date : 2025-01-15 DOI:10.1096/fj.202401903R

Miaomiao Liu, Peiquan Zhao, Huazhang Feng, Yuan Yang, Xuerui Zhang, Enguang Chen, Haodong Xiao, Jia Luo, Han Chen, Jiawei Yin, Min Lin, Ruixue Mao, Xingping Zhu, Jing Li, Ping Fei

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引用次数: 0

Abstract

Retinal pathological angiogenesis (PA) is a common hallmark in proliferative retinopathies, including age-related macular degeneration (AMD), proliferative diabetic retinopathy (PDR), and retinopathy of prematurity (ROP). The mechanisms underlying PA is complex and incompletely understood. In this study, we investigated the role of extracellular matrix (ECM) protein biglycan (BGN) in PA using an oxygen-induced retinopathy (OIR) mouse model, along with hypoxia (1% O₂) conditions for incubating pericytes and endothelial cells in vitro. We found a significant upregulation of Bgn in the retinas of OIR mice. Intravitreal injection of Bgn-specific small interfering RNA (siRNA) in OIR mice at postnatal day 12 (P12) effectively curbed retinal PA at P17. Using cultured cells, we found that BGN expression in pericytes was highly sensitive to hypoxic stimulation compared to endothelial cells. We further showed that BGN stimulated retinal PA via the upregulation of C-X-C motif chemokine ligand 12 (CXCL12). Inhibition of the CXCL12-CXCR4 axis effectively diminished PA in OIR mouse. In conclusion, our study demonstrated the stimulatory role of BGN in retinal PA, identified the link between BGN and CXCL12 expression, and further highlighted the role of pericytes in retinal PA.

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来源期刊

The FASEB Journal 生物-生化与分子生物学

CiteScore

9.20

自引率

2.10%

发文量

6243

审稿时长

3 months

期刊介绍： The FASEB Journal publishes international, transdisciplinary research covering all fields of biology at every level of organization: atomic, molecular, cell, tissue, organ, organismic and population. While the journal strives to include research that cuts across the biological sciences, it also considers submissions that lie within one field, but may have implications for other fields as well. The journal seeks to publish basic and translational research, but also welcomes reports of pre-clinical and early clinical research. In addition to research, review, and hypothesis submissions, The FASEB Journal also seeks perspectives, commentaries, book reviews, and similar content related to the life sciences in its Up Front section.