Silencing the Cytoskeleton Protein Iba1 (Ionized Calcium Binding Adapter Protein 1) Interferes with BV2 Microglia Functioning

沉默细胞骨架蛋白 Iba1(离子钙结合衔接蛋白 1)会干扰 BV2 小胶质细胞的功能

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作者:Roxana-Olimpia Gheorghe, Alexandru Deftu, Alexandru Filippi, Andreea Grosu, Melania Bica-Popi, Marioara Chiritoiu, Gabriela Chiritoiu, Cristian Munteanu, Luigi Silvestro, Violeta Ristoiu

Abstract

Iba1 (ionized calcium binding adapter protein 1) is a cytoskeleton protein specific only for microglia and macrophages, where it acts as an actin-cross linking protein. Although frequently regarded as a marker of activation, its involvement in cell migration, membrane ruffling, phagocytosis or in microglia remodeling during immunological surveillance of the brain suggest that Iba1 is not a simple cytoskeleton protein, but a signaling molecule involved in specific signaling pathways. In this study we investigated if Iba1 could also represent a drug target, and tested the hypothesis that its specific silencing with customized Iba1-siRNA can modulate microglia functioning. The results showed that Iba1-silenced BV2 microglia migrate less due to reduced proliferation and cell adhesion, while their phagocytic activity and P2x7 functioning was significantly increased. Our data are the proof of concept that Iba1 protein is a new microglia target, which opens a new therapeutic avenue for modulating microglia behavior.

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