Pericytes promote vessel stability and their dysfunction causes pathologies due to blood vessel leakage. Previously, we reported that Olfactomedin‐like 3 (Olfml3) is a matricellular protein with proangiogenic properties. Here, we explored the role of Olfml3 in a knockout mouse model engineered to suppress this protein. The mutant mice exhibited vascular defects in pericyte coverage, suggesting that pericytes influence blood vessel formation in an Olfml3‐dependent manner. Olfml3‐deficient mice exhibited abnormalities in the vasculature causing partial lethality of embryos and neonates. Reduced pericyte coverage was observed at embryonic day 12.5 and persisted throughout development, resulting in perinatal death of 35% of Olfml3‐deficient mice. Cultured Olfml3‐deficient pericytes exhibited aberrant motility and altered pericyte association to endothelial cells. Furthermore, the proliferative response of Olfml3−/− pericytes upon PDGF‐B stimulation was significantly diminished. Subsequent experiments revealed that intact PDGF‐B signaling, mediated via Olfml3 binding, is required for pericyte proliferation and activation of downstream kinase pathways. Our findings suggest a model wherein pericyte recruitment to endothelial cells requires Olfml3 to provide early instructive cue and retain PDGF‐B along newly formed vessels to achieve optimal angiogenesis.

中文翻译：

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类气味调节蛋白 3 在胚胎血管形成过程中促进 PDGF 依赖性周细胞增殖和迁移

周细胞促进血管稳定性，它们的功能障碍会导致血管渗漏引起的病变。以前，我们报道了嗅觉调节蛋白样 3 (Olfml3) 是一种具有促血管生成特性的基质细胞蛋白。在这里，我们探索了 Olfml3 在设计用于抑制这种蛋白质的基因敲除小鼠模型中的作用。突变小鼠在周细胞覆盖率方面表现出血管缺陷，表明周细胞以依赖 Olfml3 的方式影响血管形成。Olfml3 缺陷小鼠的血管系统异常，导致胚胎和新生儿部分致死。在胚胎第 12.5 天观察到周细胞覆盖率降低，并在整个发育过程中持续存在，导致 35% 的 Olfml3 缺陷小鼠围产期死亡。培养的 Olfml3 缺陷的周细胞表现出异常的运动性和改变的周细胞与内皮细胞的关联。此外，Olfml3-/- 周细胞对 PDGF-B 刺激的增殖反应显着减弱。随后的实验表明，周细胞增殖和下游激酶通路的激活需要通过 Olfml3 结合介导的完整 PDGF-B 信号传导。我们的研究结果提出了一个模型，其中内皮细胞的周细胞募集需要 Olfml3 来提供早期指导性线索并沿新形成的血管保留 PDGF-B 以实现最佳血管生成。是周细胞增殖和下游激酶通路激活所必需的。我们的研究结果提出了一个模型，其中内皮细胞的周细胞募集需要 Olfml3 来提供早期指导性线索并沿新形成的血管保留 PDGF-B 以实现最佳血管生成。是周细胞增殖和下游激酶通路激活所必需的。我们的研究结果提出了一个模型，其中内皮细胞的周细胞募集需要 Olfml3 来提供早期指导性线索并沿新形成的血管保留 PDGF-B 以实现最佳血管生成。