The Antioxidative Role of Cytoglobin in Podocytes: Implications for a Role in Chronic Kidney Disease
Publication: Antioxidants & Redox Signaling
Volume 32, Issue Number 16
Abstract
Aims: Cytoglobin (CYGB) is a member of the mammalian globin family of respiratory proteins. Despite extensive research efforts, its physiological role remains largely unknown, but potential functions include reactive oxygen species (ROS) detoxification and signaling. Accumulating evidence suggests that ROS play a crucial role in podocyte detachment and apoptosis during diabetic kidney disease. This study aimed to explore the potential antioxidative renal role of CYGB both in vivo and in vitro.
Results: Using a Cygb-deficient mouse model, we demonstrate a Cygb-dependent reduction in renal function, coinciding with a reduced number of podocytes. To specifically assess the putative antioxidative function of CYGB in podocytes, we first confirmed high endogenous CYGB expression levels in two human podocyte cell lines and subsequently generated short hairpin RNA-mediated stable CYGB knockdown podocyte models. CYGB-deficient podocytes displayed increased cell death and accumulation of ROS as assessed by 2′7′-dichlorodihydrofluorescein diacetate assays and the redox-sensitive probe roGFP2-Orp1. CYGB-deficient cells also exhibited an impaired cellular bioenergetic status. Consistently, analysis of the CYGB-dependent transcriptome identified dysregulation of multiple genes involved in redox balance, apoptosis, as well as in chronic kidney disease (CKD). Finally, genome-wide association studies and expression studies in nephropathy biopsies indicate an association of CYGB with CKD.
Innovation: This study demonstrates a podocyte-related renal role of Cygb, confirms abundant CYGB expression in human podocyte cell lines, and describes for the first time an association between CYGB and CKD.
Conclusion: Our results provide evidence for an antioxidative role of CYGB in podocytes.
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Information & Authors
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Published In
Antioxidants & Redox Signaling
Volume 32 • Issue Number 16 • June 1, 2020
Pages: 1155 - 1171
PubMed: 31910047
Copyright
Copyright 2020, Mary Ann Liebert, Inc., publishers.
History
Published in print: June 1, 2020
Published online: 28 April 2020
Published ahead of print: 6 February 2020
Published ahead of production: 7 January 2020
Accepted: 18 December 2019
Revision received: 28 November 2019
Received: 6 September 2019
Authors
Author Disclosure Statement
No competing financial interests exist.
Funding Information
This work was supported by the Swiss National Science Foundation (grant 173000) and the German Research Foundation (grant HO5837/1-1) to D.H., a University Research Priority Program “Integrative Human Physiology” grant to E.B.R., the Biobank ERCB-KFB (Else Kröner-Fresenius-Foundation) to C.D.C., an intramural grant (Center for Computer Sciences, JGU Mainz) to T.H., the International PhD Program (IMB Mainz) to E.P. and T.H., a Grant-in-Aid for Scientific Research from JSPS (No. 25293177 and No. 16H05290) and a Grant for Research Program on Hepatitis from the Japan Agency for Medical Research and Development (18fk0210004h0003) to N.K., and the NCCR Kidney.CH financed by the SNF to C.D.C., O.D., A.O., R.H.W., and D.H.
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