Date: Saturday, June 1, 2019
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall C & D
*Purpose: Although it is usually accepted that the kidney is prone to hypoxic injury, the importance of hypoxia in chronic kidney disease (CKD) as well as chronic allograft nephropathy (CAN) is not well understood. Cytoglobin (Cygb) is a non-canonical – oxygen-binding – hemoglobin expressed in the kidney, which potentially represents a novel hypoxia responsive system. However, the contribution of Cygb to hypoxic events in the kidney and CKD is unknown. The goal of the present study was to characterize the temporal and spatial expression of Cygb in a mouse model of kidney ischemia-reperfusion (IR) and to establish its functional contribution.
*Methods: Mouse LacZ-reporter systems, multiplexing immunofluorescence, and Western blot were developed to establish tissue expression and cellular localization of Cygb. Wild-type and Cygb knockout mice underwent unilateral ischemia/reperfusion injury with 30 minutes of ischemia and 1-3 weeks of recovery. Western blot, qPCR, immunohistochemistry and immunofluorescence were used to examine the development of kidney fibrosis after IR.
*Results: We established that a previously uncharacterized truncated variant of Cygb is expressed in the mouse kidney. Broad expression of Cygb in intact kidneys was evident with strong association with glomerular structures. Following IR-injury, mRNA and protein levels of this novel Cygb variant increased. Most significantly, loss of Cygb in the setting of IR-injury, led to an increase in markers for epithelial to mesenchymal transition and fibrosis.
*Conclusions: We have established that kidneys express a previously uncharacterized variant of Cygb and that its expression persist following IR. We propose that Cygb is an important regulator of renal damage following ischemic injury through regulation of epithelial to mesenchymal transition and tissue fibrosis.
To cite this abstract in AMA style:Patel D, Divanyan T, Acosta E, Carnes K, Howard D, Jourd’heuil F, Jourd’heuil D, Lopez-Soler R. Determining the Molecular Nature and Role of Cytoglobin in Chronic Allograft Nephropathy [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/determining-the-molecular-nature-and-role-of-cytoglobin-in-chronic-allograft-nephropathy/. Accessed September 19, 2020.
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