Gasdermin D-deficient mice are hypersensitive to acute kidney injury
Signaling pathways of regulated necrosis, such as necroptosis and ferroptosis, contribute to acute kidney injury (AKI), but the role of pyroptosis is unclear. Pyroptosis is mediated by the pore-forming protein gasdermin D (GSDMD). Here, we report a specific pattern of GSDMD-protein expression in the...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2023
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| Online Access: | https://hdl.handle.net/10356/171278 |
| _version_ | 1811681807926558720 |
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| author | Tonnus, Wulf Maremonti, Francesca Belavgeni, Alexia Latk, Markus Kusunoki, Yoshihiro Brucker, Anne Mässenhausen, Anne von Meyer, Claudia Locke, Sophie Gembardt, Florian Beer, Kristina Hoppenz, Paul Becker, Jan U. Hugo, Christian Anders, Hans-Joachim Bornstein, Stefan R. Shao, Feng Linkermann, Andreas |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Tonnus, Wulf Maremonti, Francesca Belavgeni, Alexia Latk, Markus Kusunoki, Yoshihiro Brucker, Anne Mässenhausen, Anne von Meyer, Claudia Locke, Sophie Gembardt, Florian Beer, Kristina Hoppenz, Paul Becker, Jan U. Hugo, Christian Anders, Hans-Joachim Bornstein, Stefan R. Shao, Feng Linkermann, Andreas |
| author_sort | Tonnus, Wulf |
| collection | NTU |
| description | Signaling pathways of regulated necrosis, such as necroptosis and ferroptosis, contribute to acute kidney injury (AKI), but the role of pyroptosis is unclear. Pyroptosis is mediated by the pore-forming protein gasdermin D (GSDMD). Here, we report a specific pattern of GSDMD-protein expression in the peritubular compartment of mice that underwent bilateral ischemia and reperfusion injury (IRI). Along similar lines, the GSDMD-protein expression in whole kidney lysates increased during the first 84 h following cisplatin-induced AKI. Importantly, unlike whole kidney lysates, no GSDMD-protein expression was detectable in isolated kidney tubules. In IRI and cisplatin-induced AKI, GSDMD-deficient mice exhibited hypersensitivity to injury as assessed by tubular damage, elevated markers of serum urea, and serum creatinine. This hypersensitivity was reversed by a combined deficiency of GSDMD and the necroptosis mediator mixed lineage kinase domain-like (MLKL). In conclusion, we demonstrate a non-cell autonomous role for GSDMD in protecting the tubular compartment from necroptosis-mediated damage in IRI. |
| first_indexed | 2024-10-01T03:46:49Z |
| format | Journal Article |
| id | ntu-10356/171278 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T03:46:49Z |
| publishDate | 2023 |
| record_format | dspace |
| spelling | ntu-10356/1712782023-10-29T15:37:51Z Gasdermin D-deficient mice are hypersensitive to acute kidney injury Tonnus, Wulf Maremonti, Francesca Belavgeni, Alexia Latk, Markus Kusunoki, Yoshihiro Brucker, Anne Mässenhausen, Anne von Meyer, Claudia Locke, Sophie Gembardt, Florian Beer, Kristina Hoppenz, Paul Becker, Jan U. Hugo, Christian Anders, Hans-Joachim Bornstein, Stefan R. Shao, Feng Linkermann, Andreas Lee Kong Chian School of Medicine (LKCMedicine) Science::Medicine Acute Kidney Tubule Necrosis Renal Ischemia Reperfusion Injury Signaling pathways of regulated necrosis, such as necroptosis and ferroptosis, contribute to acute kidney injury (AKI), but the role of pyroptosis is unclear. Pyroptosis is mediated by the pore-forming protein gasdermin D (GSDMD). Here, we report a specific pattern of GSDMD-protein expression in the peritubular compartment of mice that underwent bilateral ischemia and reperfusion injury (IRI). Along similar lines, the GSDMD-protein expression in whole kidney lysates increased during the first 84 h following cisplatin-induced AKI. Importantly, unlike whole kidney lysates, no GSDMD-protein expression was detectable in isolated kidney tubules. In IRI and cisplatin-induced AKI, GSDMD-deficient mice exhibited hypersensitivity to injury as assessed by tubular damage, elevated markers of serum urea, and serum creatinine. This hypersensitivity was reversed by a combined deficiency of GSDMD and the necroptosis mediator mixed lineage kinase domain-like (MLKL). In conclusion, we demonstrate a non-cell autonomous role for GSDMD in protecting the tubular compartment from necroptosis-mediated damage in IRI. Published version Work in the Linkermann Lab is funded by the German Research Foundation (DFG), SFB-TRR 205, SFB-TRR 127, SPP 2306, IRTG 2251, and a Heisenberg-Professorship to AL (project number 324141047). HJA was supported by the Deutsche Forschungsgemeinschaft (AN372/16-2, 27-1, and 30-1). Open Access funding enabled and organized by Projekt DEAL 2023-10-23T07:43:30Z 2023-10-23T07:43:30Z 2022 Journal Article Tonnus, W., Maremonti, F., Belavgeni, A., Latk, M., Kusunoki, Y., Brucker, A., Mässenhausen, A. V., Meyer, C., Locke, S., Gembardt, F., Beer, K., Hoppenz, P., Becker, J. U., Hugo, C., Anders, H., Bornstein, S. R., Shao, F. & Linkermann, A. (2022). Gasdermin D-deficient mice are hypersensitive to acute kidney injury. Cell Death & Disease, 13(9), 792-. https://dx.doi.org/10.1038/s41419-022-05230-9 2041-4889 https://hdl.handle.net/10356/171278 10.1038/s41419-022-05230-9 36109515 2-s2.0-85137906361 9 13 792 en Cell Death & Disease © 2022 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. application/pdf |
| spellingShingle | Science::Medicine Acute Kidney Tubule Necrosis Renal Ischemia Reperfusion Injury Tonnus, Wulf Maremonti, Francesca Belavgeni, Alexia Latk, Markus Kusunoki, Yoshihiro Brucker, Anne Mässenhausen, Anne von Meyer, Claudia Locke, Sophie Gembardt, Florian Beer, Kristina Hoppenz, Paul Becker, Jan U. Hugo, Christian Anders, Hans-Joachim Bornstein, Stefan R. Shao, Feng Linkermann, Andreas Gasdermin D-deficient mice are hypersensitive to acute kidney injury |
| title | Gasdermin D-deficient mice are hypersensitive to acute kidney injury |
| title_full | Gasdermin D-deficient mice are hypersensitive to acute kidney injury |
| title_fullStr | Gasdermin D-deficient mice are hypersensitive to acute kidney injury |
| title_full_unstemmed | Gasdermin D-deficient mice are hypersensitive to acute kidney injury |
| title_short | Gasdermin D-deficient mice are hypersensitive to acute kidney injury |
| title_sort | gasdermin d deficient mice are hypersensitive to acute kidney injury |
| topic | Science::Medicine Acute Kidney Tubule Necrosis Renal Ischemia Reperfusion Injury |
| url | https://hdl.handle.net/10356/171278 |
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