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 journalArticle

3 Citations (Scopus)

Abstract

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 (US)
Pages (from-to)1887-1899
Number of pages13
JournalJournal of the American Society of Nephrology
Volume29
Issue number7
DOIs
StatePublished - Jul 1 2018

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Adenosine Triphosphate
Reperfusion Injury
Kidney
Carbenoxolone
Inflammation
Gap Junctions
Vascular Endothelium
Knockout Mice
Adenosine
Bone Marrow
Health
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Jankowski, J., Perry, H. M., Medina, C. B., Huang, L., Yao, J., Bajwa, A., ... Okusa, M. D. (2018). Epithelial and Endothelial Pannexin1 Channels Mediate AKI. Journal of the American Society of Nephrology, 29(7), 1887-1899. https://doi.org/10.1681/ASN.2017121306

Epithelial and Endothelial Pannexin1 Channels Mediate AKI. / Jankowski, Jakub; Perry, Heather M.; Medina, Christopher B.; Huang, Liping; Yao, Junlan; Bajwa, Amandeep; Lorenz, Ulrike M.; Rosin, Diane L.; Ravichandran, Kodi S.; Isakson, Brant E.; Okusa, Mark D.

In: Journal of the American Society of Nephrology, Vol. 29, No. 7, 01.07.2018, p. 1887-1899.

Research output: Contribution to journalArticle

Jankowski, J, Perry, HM, Medina, CB, Huang, L, Yao, J, Bajwa, A, Lorenz, UM, Rosin, DL, Ravichandran, KS, Isakson, BE & Okusa, MD 2018, 'Epithelial and Endothelial Pannexin1 Channels Mediate AKI', Journal of the American Society of Nephrology, vol. 29, no. 7, pp. 1887-1899. https://doi.org/10.1681/ASN.2017121306
Jankowski, Jakub ; Perry, Heather M. ; Medina, Christopher B. ; Huang, Liping ; Yao, Junlan ; Bajwa, Amandeep ; Lorenz, Ulrike M. ; Rosin, Diane L. ; Ravichandran, Kodi S. ; Isakson, Brant E. ; Okusa, Mark D. / Epithelial and Endothelial Pannexin1 Channels Mediate AKI. In: Journal of the American Society of Nephrology. 2018 ; Vol. 29, No. 7. pp. 1887-1899.
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