Endothelial Dysfunction Accelerates Impairment of Mitochondrial Function in Ageing Kidneys via Inflammasome Activation
Chronic kidney disease is a common problem in the elderly and is associated with increased mortality. We have reported on the role of nitric oxide, which is generated from endothelial nitric oxide synthase (eNOS), in the progression of aged kidneys. To elucidate the role of endothelial dysfunction a...
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MDPI AG
2021-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/17/9269 |
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| author | Yoshihisa Wada Reina Umeno Hajime Nagasu Megumi Kondo Atsuyuki Tokuyama Hiroyuki Kadoya Kengo Kidokoro Shun’ichiro Taniguchi Masafumi Takahashi Tamaki Sasaki Naoki Kashihara |
| author_facet | Yoshihisa Wada Reina Umeno Hajime Nagasu Megumi Kondo Atsuyuki Tokuyama Hiroyuki Kadoya Kengo Kidokoro Shun’ichiro Taniguchi Masafumi Takahashi Tamaki Sasaki Naoki Kashihara |
| author_sort | Yoshihisa Wada |
| collection | DOAJ |
| description | Chronic kidney disease is a common problem in the elderly and is associated with increased mortality. We have reported on the role of nitric oxide, which is generated from endothelial nitric oxide synthase (eNOS), in the progression of aged kidneys. To elucidate the role of endothelial dysfunction and the lack of an eNOS-NO pathway in ageing kidneys, we conducted experiments using eNOS and ASC-deficient mice. C57B/6 J mice (wild type (WT)), <i>eNOS</i> knockout (eNOS KO), and <i>ASC</i> knockout (ASC KO) mice were used in the present study. Then, eNOS/ASC double-knockout (eNOS/ASC DKO) mice were generated by crossing eNOS KO and ASC KO mice. These mice were sacrificed at 17−19 months old. The Masson positive area and the KIM-1 positive area tended to increase in eNOS KO mice, compared with WT mice, but not eNOS/ASC DKO mice. The COX-positive area was significantly reduced in eNOS KO mice, compared with WT and eNOS/ASC DKO mice. To determine whether inflammasomes were activated in infiltrating macrophages, the double staining of IL-18 and F4/80 was performed. IL-18 and F4/80 were found to be co-localised in the tubulointerstitial areas. Inflammasomes play a pivotal role in inflammaging in ageing kidneys. Furthermore, inflammasome activation may accelerate cellular senescence via mitochondrial dysfunction. The importance of endothelial function as a regulatory mechanism suggests that protection of endothelial function may be a potential therapeutic target. |
| first_indexed | 2024-03-10T08:11:56Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T08:11:56Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-addac471dfab480190cdda06a2aad08d2023-11-22T10:40:44ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012217926910.3390/ijms22179269Endothelial Dysfunction Accelerates Impairment of Mitochondrial Function in Ageing Kidneys via Inflammasome ActivationYoshihisa Wada0Reina Umeno1Hajime Nagasu2Megumi Kondo3Atsuyuki Tokuyama4Hiroyuki Kadoya5Kengo Kidokoro6Shun’ichiro Taniguchi7Masafumi Takahashi8Tamaki Sasaki9Naoki Kashihara10Department of Nephrology and Hypertension, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Okayama, JapanDepartment of Nephrology and Hypertension, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Okayama, JapanDepartment of Nephrology and Hypertension, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Okayama, JapanDepartment of Nephrology and Hypertension, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Okayama, JapanDepartment of Nephrology and Hypertension, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Okayama, JapanDepartment of Nephrology and Hypertension, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Okayama, JapanDepartment of Nephrology and Hypertension, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Okayama, JapanDepartment of Hematology and Medical Oncology, Shinshu University Graduate School of Medicine, Matsumoto 390-8621, Nagano, JapanDivision of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Shimotsuke 329-0498, Tochigi, JapanDepartment of Nephrology and Hypertension, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Okayama, JapanDepartment of Nephrology and Hypertension, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Okayama, JapanChronic kidney disease is a common problem in the elderly and is associated with increased mortality. We have reported on the role of nitric oxide, which is generated from endothelial nitric oxide synthase (eNOS), in the progression of aged kidneys. To elucidate the role of endothelial dysfunction and the lack of an eNOS-NO pathway in ageing kidneys, we conducted experiments using eNOS and ASC-deficient mice. C57B/6 J mice (wild type (WT)), <i>eNOS</i> knockout (eNOS KO), and <i>ASC</i> knockout (ASC KO) mice were used in the present study. Then, eNOS/ASC double-knockout (eNOS/ASC DKO) mice were generated by crossing eNOS KO and ASC KO mice. These mice were sacrificed at 17−19 months old. The Masson positive area and the KIM-1 positive area tended to increase in eNOS KO mice, compared with WT mice, but not eNOS/ASC DKO mice. The COX-positive area was significantly reduced in eNOS KO mice, compared with WT and eNOS/ASC DKO mice. To determine whether inflammasomes were activated in infiltrating macrophages, the double staining of IL-18 and F4/80 was performed. IL-18 and F4/80 were found to be co-localised in the tubulointerstitial areas. Inflammasomes play a pivotal role in inflammaging in ageing kidneys. Furthermore, inflammasome activation may accelerate cellular senescence via mitochondrial dysfunction. The importance of endothelial function as a regulatory mechanism suggests that protection of endothelial function may be a potential therapeutic target.https://www.mdpi.com/1422-0067/22/17/9269inflammasomesenescence-associated secretory phenotypemacrophagesmitochondria dysfunctionASC-deficient mice |
| spellingShingle | Yoshihisa Wada Reina Umeno Hajime Nagasu Megumi Kondo Atsuyuki Tokuyama Hiroyuki Kadoya Kengo Kidokoro Shun’ichiro Taniguchi Masafumi Takahashi Tamaki Sasaki Naoki Kashihara Endothelial Dysfunction Accelerates Impairment of Mitochondrial Function in Ageing Kidneys via Inflammasome Activation International Journal of Molecular Sciences inflammasome senescence-associated secretory phenotype macrophages mitochondria dysfunction ASC-deficient mice |
| title | Endothelial Dysfunction Accelerates Impairment of Mitochondrial Function in Ageing Kidneys via Inflammasome Activation |
| title_full | Endothelial Dysfunction Accelerates Impairment of Mitochondrial Function in Ageing Kidneys via Inflammasome Activation |
| title_fullStr | Endothelial Dysfunction Accelerates Impairment of Mitochondrial Function in Ageing Kidneys via Inflammasome Activation |
| title_full_unstemmed | Endothelial Dysfunction Accelerates Impairment of Mitochondrial Function in Ageing Kidneys via Inflammasome Activation |
| title_short | Endothelial Dysfunction Accelerates Impairment of Mitochondrial Function in Ageing Kidneys via Inflammasome Activation |
| title_sort | endothelial dysfunction accelerates impairment of mitochondrial function in ageing kidneys via inflammasome activation |
| topic | inflammasome senescence-associated secretory phenotype macrophages mitochondria dysfunction ASC-deficient mice |
| url | https://www.mdpi.com/1422-0067/22/17/9269 |
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