The anti-oxidative role of cytoglobin in podocytes: implications for a role in chronic kidney disease
| Autor: | Elena Porto, Csaba Szabó, Sylvia Dewilde, Olivier Devuyst, Andreas D. Kistler, Elisa B. Randi, Clemens D. Cohen, Roland H. Wenger, Maja T. Lindenmeyer, Alex Odermatt, Thomas Hankeln, David Hoogewijs, Maria Tsachaki, Norifumi Kawada, Le Thi Thanh Thuy, Benjamin A. Vervaet, Stijn Vermeylen |
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| Přispěvatelé: | University of Zurich, Hoogewijs, David, UCL - SSS/IREC/NEFR - Pôle de Néphrologie |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Programmed cell death 1303 Biochemistry Cell Survival Physiology Clinical Biochemistry 610 Medicine & health Biology 1308 Clinical Biochemistry medicine.disease_cause Biochemistry Antioxidants Podocyte Nephropathy 10052 Institute of Physiology Transcriptome Diabetic nephropathy 1307 Cell Biology 03 medical and health sciences Mice medicine 1312 Molecular Biology Animals Humans Renal Insufficiency Chronic Molecular Biology Cells Cultured General Environmental Science Mice Knockout Gene knockdown 030102 biochemistry & molecular biology Podocytes Cytoglobin 1314 Physiology Cell Biology medicine.disease Cell biology Mice Inbred C57BL Chemistry Disease Models Animal 030104 developmental biology medicine.anatomical_structure General Earth and Planetary Sciences 570 Life sciences biology Human medicine Oxidative stress |
| Zdroj: | Antioxidants and redox signaling Antioxidants & Redox Signaling, Vol. 32, no.16, p. 1155-1171 (2020) |
| ISSN: | 1557-7716 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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