GDF-15 Suppresses Puromycin Aminonucleoside-Induced Podocyte Injury by Reducing Endoplasmic Reticulum Stress and Glomerular Inflammation
GDF15, also known as MIC1, is a member of the TGF-beta superfamily. Previous studies reported elevated serum levels of GDF15 in patients with kidney disorder, and its association with kidney disease progression, while other studies identified GDF15 to have protective effects. To investigate the pote...
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MDPI AG
2024-04-01
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| author | Ekaterina von Rauchhaupt Martin Klaus Andrea Ribeiro Mohsen Honarpisheh Chenyu Li Min Liu Paulina Köhler Karina Adamowicz Christoph Schmaderer Maja Lindenmeyer Stefanie Steiger Hans-Joachim Anders Maciej Lech |
| author_facet | Ekaterina von Rauchhaupt Martin Klaus Andrea Ribeiro Mohsen Honarpisheh Chenyu Li Min Liu Paulina Köhler Karina Adamowicz Christoph Schmaderer Maja Lindenmeyer Stefanie Steiger Hans-Joachim Anders Maciej Lech |
| author_sort | Ekaterina von Rauchhaupt |
| collection | DOAJ |
| description | GDF15, also known as MIC1, is a member of the TGF-beta superfamily. Previous studies reported elevated serum levels of GDF15 in patients with kidney disorder, and its association with kidney disease progression, while other studies identified GDF15 to have protective effects. To investigate the potential protective role of GDF15 on podocytes, we first performed in vitro studies using a <i>Gdf15</i>-deficient podocyte cell line. The lack of GDF15 intensified puromycin aminonucleoside (PAN)-triggered endoplasmic reticulum stress and induced cell death in cultivated podocytes. This was evidenced by elevated expressions of <i>Xbp1</i> and ER-associated chaperones, alongside AnnexinV/PI staining and LDH release. Additionally, we subjected mice to nephrotoxic PAN treatment. Our observations revealed a noteworthy increase in both GDF15 expression and secretion subsequent to PAN administration. <i>Gdf15</i> knockout mice displayed a moderate loss of WT1+ cells (podocytes) in the glomeruli compared to wild-type controls. However, this finding could not be substantiated through digital evaluation. The parameters of kidney function, including serum BUN, creatinine, and albumin–creatinine ratio (ACR), were increased in <i>Gdf15</i> knockout mice as compared to wild-type mice upon PAN treatment. This was associated with an increase in the number of glomerular macrophages, neutrophils, inflammatory cytokines, and chemokines in <i>Gdf15</i>-deficient mice. In summary, our findings unveil a novel renoprotective effect of GDF15 during kidney injury and inflammation by promoting podocyte survival and regulating endoplasmic reticulum stress in podocytes, and, subsequently, the infiltration of inflammatory cells via paracrine effects on surrounding glomerular cells. |
| first_indexed | 2024-04-24T10:47:25Z |
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| language | English |
| last_indexed | 2024-04-24T10:47:25Z |
| publishDate | 2024-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-1dc1302766904dadb68607b1cf59bd622024-04-12T13:16:36ZengMDPI AGCells2073-44092024-04-0113763710.3390/cells13070637GDF-15 Suppresses Puromycin Aminonucleoside-Induced Podocyte Injury by Reducing Endoplasmic Reticulum Stress and Glomerular InflammationEkaterina von Rauchhaupt0Martin Klaus1Andrea Ribeiro2Mohsen Honarpisheh3Chenyu Li4Min Liu5Paulina Köhler6Karina Adamowicz7Christoph Schmaderer8Maja Lindenmeyer9Stefanie Steiger10Hans-Joachim Anders11Maciej Lech12Department of Medicine IV, Renal Division, Ludwig-Maximilians-University Hospital, Ludwig-Maximilians-University Munich, 80336 Munich, GermanyDepartment of Medicine IV, Renal Division, Ludwig-Maximilians-University Hospital, Ludwig-Maximilians-University Munich, 80336 Munich, GermanyDepartment of Medicine IV, Renal Division, Ludwig-Maximilians-University Hospital, Ludwig-Maximilians-University Munich, 80336 Munich, GermanyDepartment of Medicine IV, Renal Division, Ludwig-Maximilians-University Hospital, Ludwig-Maximilians-University Munich, 80336 Munich, GermanyDepartment of Medicine IV, Renal Division, Ludwig-Maximilians-University Hospital, Ludwig-Maximilians-University Munich, 80336 Munich, GermanyDepartment of Medicine IV, Renal Division, Ludwig-Maximilians-University Hospital, Ludwig-Maximilians-University Munich, 80336 Munich, GermanyDepartment of Medicine IV, Renal Division, Ludwig-Maximilians-University Hospital, Ludwig-Maximilians-University Munich, 80336 Munich, GermanyDepartment of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology of Jagiellonian University, 30-387 Krakow, PolandKlinikum Rechts der Isar, Department of Nephrology, Technical University Munich, 81675 Munich, GermanyIII Department of Medicine, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, GermanyDepartment of Medicine IV, Renal Division, Ludwig-Maximilians-University Hospital, Ludwig-Maximilians-University Munich, 80336 Munich, GermanyDepartment of Medicine IV, Renal Division, Ludwig-Maximilians-University Hospital, Ludwig-Maximilians-University Munich, 80336 Munich, GermanyDepartment of Medicine IV, Renal Division, Ludwig-Maximilians-University Hospital, Ludwig-Maximilians-University Munich, 80336 Munich, GermanyGDF15, also known as MIC1, is a member of the TGF-beta superfamily. Previous studies reported elevated serum levels of GDF15 in patients with kidney disorder, and its association with kidney disease progression, while other studies identified GDF15 to have protective effects. To investigate the potential protective role of GDF15 on podocytes, we first performed in vitro studies using a <i>Gdf15</i>-deficient podocyte cell line. The lack of GDF15 intensified puromycin aminonucleoside (PAN)-triggered endoplasmic reticulum stress and induced cell death in cultivated podocytes. This was evidenced by elevated expressions of <i>Xbp1</i> and ER-associated chaperones, alongside AnnexinV/PI staining and LDH release. Additionally, we subjected mice to nephrotoxic PAN treatment. Our observations revealed a noteworthy increase in both GDF15 expression and secretion subsequent to PAN administration. <i>Gdf15</i> knockout mice displayed a moderate loss of WT1+ cells (podocytes) in the glomeruli compared to wild-type controls. However, this finding could not be substantiated through digital evaluation. The parameters of kidney function, including serum BUN, creatinine, and albumin–creatinine ratio (ACR), were increased in <i>Gdf15</i> knockout mice as compared to wild-type mice upon PAN treatment. This was associated with an increase in the number of glomerular macrophages, neutrophils, inflammatory cytokines, and chemokines in <i>Gdf15</i>-deficient mice. In summary, our findings unveil a novel renoprotective effect of GDF15 during kidney injury and inflammation by promoting podocyte survival and regulating endoplasmic reticulum stress in podocytes, and, subsequently, the infiltration of inflammatory cells via paracrine effects on surrounding glomerular cells.https://www.mdpi.com/2073-4409/13/7/637GDF15podocytesendoplasmic reticulum stresspodocytopathiesglomerular inflammation |
| spellingShingle | Ekaterina von Rauchhaupt Martin Klaus Andrea Ribeiro Mohsen Honarpisheh Chenyu Li Min Liu Paulina Köhler Karina Adamowicz Christoph Schmaderer Maja Lindenmeyer Stefanie Steiger Hans-Joachim Anders Maciej Lech GDF-15 Suppresses Puromycin Aminonucleoside-Induced Podocyte Injury by Reducing Endoplasmic Reticulum Stress and Glomerular Inflammation Cells GDF15 podocytes endoplasmic reticulum stress podocytopathies glomerular inflammation |
| title | GDF-15 Suppresses Puromycin Aminonucleoside-Induced Podocyte Injury by Reducing Endoplasmic Reticulum Stress and Glomerular Inflammation |
| title_full | GDF-15 Suppresses Puromycin Aminonucleoside-Induced Podocyte Injury by Reducing Endoplasmic Reticulum Stress and Glomerular Inflammation |
| title_fullStr | GDF-15 Suppresses Puromycin Aminonucleoside-Induced Podocyte Injury by Reducing Endoplasmic Reticulum Stress and Glomerular Inflammation |
| title_full_unstemmed | GDF-15 Suppresses Puromycin Aminonucleoside-Induced Podocyte Injury by Reducing Endoplasmic Reticulum Stress and Glomerular Inflammation |
| title_short | GDF-15 Suppresses Puromycin Aminonucleoside-Induced Podocyte Injury by Reducing Endoplasmic Reticulum Stress and Glomerular Inflammation |
| title_sort | gdf 15 suppresses puromycin aminonucleoside induced podocyte injury by reducing endoplasmic reticulum stress and glomerular inflammation |
| topic | GDF15 podocytes endoplasmic reticulum stress podocytopathies glomerular inflammation |
| url | https://www.mdpi.com/2073-4409/13/7/637 |
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