Pathological ocular angiogenesis has long been associated with myeloid cell activation. However, the precise cellular and molecular mechanisms governing the intricate crosstalk between the immune system and vascular changes during ocular neovascularization formation remain elusive. In this study, we demonstrated that the absence of the suppressor of cytokine signaling 3 (SOCS3) in myeloid cells led to a substantial accumulation of microglia and macrophage subsets during the neovascularization process. Our single-cell RNA sequencing data analysis revealed a remarkable increase in the expression of the secreted phosphoprotein 1 () gene within these microglia and macrophages, identifying subsets of -expressing microglia and macrophages during neovascularization formation in angiogenesis mouse models. Notably, the number of -expressing microglia and macrophages exhibited further elevation during neovascularization in mice lacking myeloid SOCS3. Moreover, our investigation unveiled the gene as a direct transcriptional target gene of signal transducer and activator of transcription 3. Importantly, pharmaceutical activation of SOCS3 or blocking of SPP1 resulted in a significant reduction in pathological neovascularization. In conclusion, our study highlights the pivotal role of the SOCS3/STAT3/SPP1 axis in the regulation of pathological retinal angiogenesis.

中文翻译：

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SOCS3通过调节小胶质细胞和巨噬细胞中SPP1的表达来调节病理性视网膜血管生成

病理性眼部血管生成长期以来一直与骨髓细胞活化有关。然而，控制眼部新生血管形成过程中免疫系统和血管变化之间复杂串扰的精确细胞和分子机制仍然难以捉摸。在这项研究中，我们证明骨髓细胞中细胞因子信号传导抑制因子 3 (SOCS3) 的缺失导致新血管形成过程中小胶质细胞和巨噬细胞亚群的大量积累。我们的单细胞 RNA 测序数据分析显示，这些小胶质细胞和巨噬细胞内分泌型磷蛋白 1 () 基因的表达显着增加，从而识别了血管生成小鼠模型中新血管形成过程中表达小胶质细胞和巨噬细胞的子集。值得注意的是，在缺乏骨髓SOCS3的小鼠的新血管形成过程中，表达β的小胶质细胞和巨噬细胞的数量表现出进一步升高。此外，我们的研究揭示了该基因作为信号转导子和转录激活子3的直接转录靶基因。重要的是，药物激活SOCS3或阻断SPP1导致病理性新生血管形成显着减少。总之，我们的研究强调了 SOCS3/STAT3/SPP1 轴在病理性视网膜血管生成调节中的关键作用。