Peptide Lv augments intermediate-conductance calcium-dependent potassium channels (KCa3.1) in endothelial cells to promote angiogenesis.
Peptide Lv augments intermediate-conductance calcium-dependent potassium channels (KCa3.1) in endothelial cells to promote angiogenesis.
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DOI：
10.1371/journal.pone.0276744
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发表时间：
2022
期刊：
影响因子：
3.7
通讯作者：
Ko, Gladys Y. P.
中科院分区：
文献类型：
--
作者：
Pham, Dylan L.;Niemi, Autumn;Ko, Michael L.;Ko, Gladys Y. P.
Lv肽是一种小的内源性分泌肽，在各种组织中表达，并在不同物种中保守。患有糖尿病视网膜病变（一种具有病理性血管生成的眼部疾病）的患者在其视网膜中具有上调的肽Lv。Lv肽的促血管生成活性部分是通过促进血管内皮细胞（EC）的增殖、迁移和出芽来实现的，但其分子机制尚不完全清楚。本研究旨在通过膜片钳电生理记录、Western免疫印迹、定量PCR和细胞增殖试验，在体外培养的内皮细胞中，阐明Lv肽如何促进内皮细胞依赖的血管生成。用肽Lv处理的内皮细胞变得显著超极化，这是EC激活的重要步骤。用肽Lv处理增强了有助于EC超极化的中间电导钙依赖性钾（KCa3.1）通道的表达和电流密度，但没有增强其他钾通道。阻断KCa3.1可减弱Lv肽诱导的EC增殖。这些结果表明，肽LV刺激的EC中功能性KCa 3.1的增加有助于EC活化和EC依赖性血管生成。
Peptide Lv is a small endogenous secretory peptide that is expressed in various tissues and conserved across different species. Patients with diabetic retinopathy, an ocular disease with pathological angiogenesis, have upregulated peptide Lv in their retinas. The pro-angiogenic activity of peptide Lv is in part through promoting vascular endothelial cell (EC) proliferation, migration, and sprouting, but its molecular mechanism is not completely understood. This study aimed to decipher how peptide Lv promotes EC-dependent angiogenesis by using patch-clamp electrophysiological recordings, Western immunoblotting, quantitative PCR, and cell proliferation assays in cultured ECs. Endothelial cells treated with peptide Lv became significantly hyperpolarized, an essential step for EC activation. Treatment with peptide Lv augmented the expression and current densities of the intermediate-conductance calcium-dependent potassium (KCa3.1) channels that contribute to EC hyperpolarization but did not augment other potassium channels. Blocking KCa3.1 attenuated peptide Lv-elicited EC proliferation. These results indicate that peptide Lv-stimulated increases of functional KCa3.1 in ECs contributes to EC activation and EC-dependent angiogenesis.
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