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Sci Rep. 2019 Jun 20;9(1):8888. doi: 10.1038/s41598-019-45303-y.

Coro2b, a podocyte protein downregulated in human diabetic nephropathy, is involved in the development of protamine sulphate-induced foot process effacement.

Author information

1
Karolinska Institutet/AstraZeneca Integrated Cardio Metabolic Centre, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
2
Science for Life Laboratory, Department of Applied Physics, Royal Institute of Technology, Solna, Sweden.
3
Division of Renal Medicine, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
4
Bioscience, Cardiovascular, Renal and Metabolism, Innovative Medicines Biotech Unit, AstraZeneca, Gothenburg, Sweden.
5
Karolinska Institutet/AstraZeneca Integrated Cardio Metabolic Centre, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden. jaakko.patrakka@ki.se.

Abstract

Podocytes have an important role in the pathogenesis of diabetic nephropathy (DN). Podocyte foot process effacement, mediated largely by the actin-based cytoskeleton of foot processes, is commonly detected in DN and is believed to be a key pathogenic event in the development of proteinuria. In this study, we identified coronin 2b (Coro2b), a member of known actin-regulating proteins, the coronins, as a highly podocyte-enriched molecule located at the cytoplasmic side of the apical plasma membrane. Studies in human renal biopsies show that glomerular Coro2b expression is significantly down-regulated in patients with DN. Studies in knockout mice indicate that Coro2b is not required for the development or maintenance of the glomerular filtration barrier. Moreover, inactivation of Coro2b specifically in podocytes does not affect the outcome of nephropathy in a streptozotocin-induced diabetes model. However, Coro2b seems to modulate the reorganization of foot processes under pathological conditions as Coro2b knockout podocytes are partially protected from protamine sulfate perfusion-induced foot process effacement. Taken together, our study suggests a role for Coro2b in the pathogenesis of glomerulopathies. Further studies regarding the involvement of Coro2b in podocyte health and diseases are warranted.

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