CD73 Overexpression in Podocytes: A Novel Marker of Podocyte Injury in Human Kidney Disease

• Main Authors: Zoran V. Popovic, Felix Bestvater, Damir Krunic, Bernhard K. Krämer, Raoul Bergner, Christian Löffler, Berthold Hocher, Alexander Marx, Stefan Porubsky
• Format: Article
• Language: English
• Published: MDPI AG 2021-07-01
• Series: International Journal of Molecular Sciences
• Subjects: podocyte; minimal change disease; CD73; CCR2
• Online Access: https://www.mdpi.com/1422-0067/22/14/7642

The CD73 pathway is an important anti-inflammatory mechanism in various disease settings. Observations in mouse models suggested that CD73 might have a protective role in kidney damage; however, no direct evidence of its role in human kidney disease has been described to date. Here, we hypothesized that podocyte injury in human kidney diseases alters CD73 expression that may facilitate the diagnosis of podocytopathies. We assessed the expression of CD73 and one of its functionally important targets, the C-C chemokine receptor type 2 (CCR2), in podocytes from kidney biopsies of 39 patients with podocytopathy (including focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranous glomerulonephritis (MGN) and amyloidosis) and a control group. Podocyte CD73 expression in each of the disease groups was significantly increased in comparison to controls (<i>p</i> < 0.001–<i>p</i> < 0.0001). Moreover, there was a marked negative correlation between CD73 and CCR2 expression, as confirmed by immunohistochemistry and immunofluorescence (Pearson r = −0.5068, <i>p</i> = 0.0031; Pearson r = −0.4705, <i>p</i> = 0.0313, respectively), thus suggesting a protective role of CD73 in kidney injury. Finally, we identify CD73 as a novel potential diagnostic marker of human podocytopathies, particularly of MCD that has been notorious for the lack of pathological features recognizable by light microscopy and immunohistochemistry.