Epithelial and Endothelial Pannexin1 Channels Mediate AKI

Jakub Jankowski, Heather M. Perry, Christopher B. Medina, Liping Huang, Junlan Yao, Amandeep Bajwa, Ulrike M. Lorenz, Diane L. Rosin, Kodi S. Ravichandran, Brant E. Isakson, Mark D. Okusa

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


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.

Original languageEnglish
Pages (from-to)1887-1899
Number of pages13
JournalJournal of the American Society of Nephrology
Issue number7
StatePublished - Jul 2018


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