内皮TGFβ信号通过髓系内皮细胞相互作用调节脉络膜新生血管的严重程度
Endothelial TGFβ signaling modulates choroidal neovascularization severity via myeloid-endothelial cell interaction.
摘要(中文译文)
血-视网膜屏障（BRB）对于维持视网膜稳态至关重要，因此其破坏会促进新生血管性年龄相关性黄斑变性（nAMD）等疾病中的病理性血管生成。脉络膜新生血管（CNV）被认为是nAMD的标志性特征。这些新形成的血管突破血-视网膜屏障，导致快速且严重的视力丧失。本研究探讨了内皮细胞TGFβ信号如何与单核吞噬细胞（MP，如小胶质细胞）相互作用以调控脉络膜新生血管。研究中，我们采用了激光诱导的CNV小鼠模型，对内皮细胞特异性敲除Tgfbr2，并通过PLX5622同时清除单核吞噬细胞。我们证明，内皮细胞TGFβ信号的缺失显著加重了CNV。引人注目的是，这一效应在清除单核吞噬细胞后被完全逆转。CNV病灶的转录组和RNA定位分析鉴定出纤维蛋白原α链（）为一种单核吞噬细胞来源的因子，其仅在内皮细胞TGFβ信号缺失的小鼠中上调。这些发现提示内皮细胞与单核吞噬细胞之间存在一种新的TGFβ依赖性相互作用，该相互作用通过小胶质细胞来源的 表达促进血管生成。
Abstract
The blood-retinal barrier (BRB) is essential for maintaining retinal homeostasis, consequently its disruption contributes to pathological angiogenesis in diseases such as neovascular age-related macular degeneration (nAMD). Choroidal neovascularization (CNV) is considered as a hallmark of nAMD. These newly formed vessels break through the BRB leading to rapid and severe vision loss. Here, we investigated how endothelial TGFβ signaling interacts with mononuclear phagocytes (MP), such as microglia to regulate choroidal neovascularization (CNV). In this study, we used a laser-induced CNV model in mice with endothelial-specific Tgfbr2 deletion and concomitant MP depletion via PLX5622. We demonstrate that loss of endothelial TGFβ signaling significantly exacerbates CNV. Strikingly, this effect is fully rescued by MP depletion. Transcriptome and RNA localization of CNV lesions identified fibrinogen alpha chain () as a MP-derived factor that is exclusively upregulated in mice without endothelial TGFβ signaling. These findings suggest a novel TGFβ-dependent interaction between endothelial cells and MP that promotes angiogenesis through microglia derived expression.
如何引用
AMA
Anja Schlecht, Lisa Müllerbauer, Katja Fitz, Bianka Brunne, Nico Hofmann, Christian Müller, et al. Endothelial TGFβ signaling modulates choroidal neovascularization severity via myeloid-endothelial cell interaction.. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1813788.
APA
Anja Schlecht, Lisa Müllerbauer, Katja Fitz, Bianka Brunne, Nico Hofmann, Christian Müller, et al (2026). Endothelial TGFβ signaling modulates choroidal neovascularization severity via myeloid-endothelial cell interaction.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1813788
GB/T 7714
Anja Schlecht, Lisa Müllerbauer, Katja Fitz, Bianka Brunne, Nico Hofmann, Christian Müller, et al. Endothelial TGFβ signaling modulates choroidal neovascularization severity via myeloid-endothelial cell interaction.[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1813788.
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