Role of volume-regulated anion channels (VRACs) in kidney integrity (B02)

我们最近发现由LRRC8异聚体形成的体积调节阴离子通道VRAC在细胞体积调节、细胞凋亡以及可能的上皮转运中发挥重要作用。VRAC破坏后的肾小管变性可以推断出VRAC在维持肾脏完整性中的重要作用。从VRAC在脑和心脏缺血中的可能作用推断，我们假设它重要地调节肾脏缺血再灌注损伤（IRI）。通过对不同小鼠模型的分析，我们将在肾脏中定位所有5个LRRC8亚基，研究它们在肾小管过程中的生理作用，并阐明它们在IRI中的作用。VRAC可能成为治疗肾损伤的新靶点。

The volume-regulated anion channel VRAC, recently identified by us to be formed by LRRC8 heteromers, has important roles in cell volume regulation, apoptosis, and probably transepithelial transport. An important role of VRAC in the maintenance of kidney integrity is inferred by renal tubular degeneration upon VRAC disruption. Extrapolating from VRAC’s likely role in brain and cardiac ischemia, we assume that it importantly modulates ischemia-reperfusion injury (IRI) in the kidney. Through analysis in different mouse models, we will localize all 5 LRRC8 subunits in the kidney, investigate their physiological roles in tubular processes, and will clarify their role in IRI. VRAC may turn out to be a novel target for treating kidney injury.