Background Pannexin1 (Panx1), an ATP release channel, is present in most mammalian tissues, but the role of Panx1 in health and disease is not fully understood. Panx1 may serve to modulate AKI; ATP is a precursor to adenosine and may function to block inflammation, or ATP may act as a danger-associated molecular pattern and initiate inflammation.Methods We used pharmacologic and genetic approaches to evaluate the effect of Panx1 on kidney ischemia-reperfusion injury (IRI), a mouse model of AKI.Results Pharmacologic inhibition of gap junctions, including Panx1, by administration of carbenoxolone protected mice from IRI. Furthermore, global deletion of Panx1 preserved kidney function and morphology and diminished the expression of proinflammatory molecules after IRI. Analysis of bone marrow chimeric mice revealed that Panx1 expressed on parenchymal cells is necessary for ischemic injury, and both proximal tubule and vascular endothelial Panx1 tissue-specific knockout mice were protected from IRI. In vitro, Panx1-deficient proximal tubule cells released less and retained more ATP under hypoxic stress.Conclusions Panx1 is involved in regulating ATP release from hypoxic cells, and reducing this ATP release may protect kidneys from AKI.

中文翻译：

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上皮和内皮Pannexin1通道介导AKI。

背景Pannexin1（Panx1）是一种ATP释放通道，存在于大多数哺乳动物组织中，但尚未完全了解Panx1在健康和疾病中的作用。Panx1可能起到调节AKI的作用；ATP是腺苷的前体，可能起到阻止炎症的作用，或者ATP可能是与危险相关的分子模式并引发炎症。 ，这是AKI的小鼠模型。结果通过给予受卡培洛酮保护的IRI小鼠，可以药理抑制包括Panx1在内的间隙连接。此外，Panx1的整体删除保留了肾脏功能和形态，并减少了IRI后促炎分子的表达。骨髓嵌合小鼠的分析显示，Panx1在实质细胞上表达对于缺血性损伤是必需的，并且近端肾小管和血管内皮Panx1组织特异性基因敲除小鼠均受到IRI保护。在缺氧条件下，缺乏Panx1的近端小管细胞在体外释放较少并保留更多的ATP。