Post-Ischemic Renal Fibrosis Progression Is Halted by Delayed Contralateral Nephrectomy: The Involvement of Macrophage Activation
(1) Background: Successful treatment of acute kidney injury (AKI)-induced chronic kidney disease (CKD) is unresolved. We aimed to characterize the time-course of changes after contralateral nephrectomy (Nx) in a model of unilateral ischemic AKI-induced CKD with good translational utility. (2) Method...
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MDPI AG
2020-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/11/3825 |
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| author | Pál Tod Eva Nora Bukosza Beáta Róka Tamás Kaucsár Attila Fintha Tibor Krenács Gábor Szénási Péter Hamar |
| author_facet | Pál Tod Eva Nora Bukosza Beáta Róka Tamás Kaucsár Attila Fintha Tibor Krenács Gábor Szénási Péter Hamar |
| author_sort | Pál Tod |
| collection | DOAJ |
| description | (1) Background: Successful treatment of acute kidney injury (AKI)-induced chronic kidney disease (CKD) is unresolved. We aimed to characterize the time-course of changes after contralateral nephrectomy (Nx) in a model of unilateral ischemic AKI-induced CKD with good translational utility. (2) Methods: Severe (30 min) left renal ischemia-reperfusion injury (IRI) or sham operation (S) was performed in male Naval Medical Research Institute (NMRI) mice followed by Nx or S one week later. Expression of proinflammatory, oxidative stress, injury and fibrotic markers was evaluated by RT-qPCR. (3) Results: Upon Nx, the injured kidney hardly functioned for three days, but it gradually regained function until day 14 to 21, as demonstrated by the plasma urea. Functional recovery led to a drastic reduction in inflammatory infiltration by macrophages and by decreases in macrophage chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-α) mRNA and most injury markers. However, without Nx, a marked upregulation of proinflammatory (TNF-α, IL-6, MCP-1 and complement-3 (C3)); oxidative stress (nuclear factor erythroid 2-related factor 2, NRF2) and fibrosis (collagen-1a1 (Col1a1) and fibronectin-1 (FN1)) genes perpetuated, and the injured kidney became completely fibrotic. Contralateral Nx delayed the development of renal failure up to 20 weeks. (4) Conclusion: Our results suggest that macrophage activation is involved in postischemic renal fibrosis, and it is drastically suppressed by contralateral nephrectomy ameliorating progression. |
| first_indexed | 2024-03-10T19:33:13Z |
| format | Article |
| id | doaj.art-e86c80d17d06480faae4e38d1a0650ad |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T19:33:13Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e86c80d17d06480faae4e38d1a0650ad2023-11-20T02:00:25ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-05-012111382510.3390/ijms21113825Post-Ischemic Renal Fibrosis Progression Is Halted by Delayed Contralateral Nephrectomy: The Involvement of Macrophage ActivationPál Tod0Eva Nora Bukosza1Beáta Róka2Tamás Kaucsár3Attila Fintha4Tibor Krenács5Gábor Szénási6Péter Hamar7Institute of Translational Medicine, Semmelweis University, 1094 Budapest, HungaryInstitute of Translational Medicine, Semmelweis University, 1094 Budapest, HungaryInstitute of Translational Medicine, Semmelweis University, 1094 Budapest, HungaryInstitute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary1st Department of Pathology and Experimental Cancer Research, Semmelweis University, 1085 Budapest, Hungary1st Department of Pathology and Experimental Cancer Research, Semmelweis University, 1085 Budapest, HungaryInstitute of Translational Medicine, Semmelweis University, 1094 Budapest, HungaryInstitute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary(1) Background: Successful treatment of acute kidney injury (AKI)-induced chronic kidney disease (CKD) is unresolved. We aimed to characterize the time-course of changes after contralateral nephrectomy (Nx) in a model of unilateral ischemic AKI-induced CKD with good translational utility. (2) Methods: Severe (30 min) left renal ischemia-reperfusion injury (IRI) or sham operation (S) was performed in male Naval Medical Research Institute (NMRI) mice followed by Nx or S one week later. Expression of proinflammatory, oxidative stress, injury and fibrotic markers was evaluated by RT-qPCR. (3) Results: Upon Nx, the injured kidney hardly functioned for three days, but it gradually regained function until day 14 to 21, as demonstrated by the plasma urea. Functional recovery led to a drastic reduction in inflammatory infiltration by macrophages and by decreases in macrophage chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-α) mRNA and most injury markers. However, without Nx, a marked upregulation of proinflammatory (TNF-α, IL-6, MCP-1 and complement-3 (C3)); oxidative stress (nuclear factor erythroid 2-related factor 2, NRF2) and fibrosis (collagen-1a1 (Col1a1) and fibronectin-1 (FN1)) genes perpetuated, and the injured kidney became completely fibrotic. Contralateral Nx delayed the development of renal failure up to 20 weeks. (4) Conclusion: Our results suggest that macrophage activation is involved in postischemic renal fibrosis, and it is drastically suppressed by contralateral nephrectomy ameliorating progression.https://www.mdpi.com/1422-0067/21/11/3825acute kidney injurychronic kidney diseaseinflammationMCP-1TNF-αmice |
| spellingShingle | Pál Tod Eva Nora Bukosza Beáta Róka Tamás Kaucsár Attila Fintha Tibor Krenács Gábor Szénási Péter Hamar Post-Ischemic Renal Fibrosis Progression Is Halted by Delayed Contralateral Nephrectomy: The Involvement of Macrophage Activation International Journal of Molecular Sciences acute kidney injury chronic kidney disease inflammation MCP-1 TNF-α mice |
| title | Post-Ischemic Renal Fibrosis Progression Is Halted by Delayed Contralateral Nephrectomy: The Involvement of Macrophage Activation |
| title_full | Post-Ischemic Renal Fibrosis Progression Is Halted by Delayed Contralateral Nephrectomy: The Involvement of Macrophage Activation |
| title_fullStr | Post-Ischemic Renal Fibrosis Progression Is Halted by Delayed Contralateral Nephrectomy: The Involvement of Macrophage Activation |
| title_full_unstemmed | Post-Ischemic Renal Fibrosis Progression Is Halted by Delayed Contralateral Nephrectomy: The Involvement of Macrophage Activation |
| title_short | Post-Ischemic Renal Fibrosis Progression Is Halted by Delayed Contralateral Nephrectomy: The Involvement of Macrophage Activation |
| title_sort | post ischemic renal fibrosis progression is halted by delayed contralateral nephrectomy the involvement of macrophage activation |
| topic | acute kidney injury chronic kidney disease inflammation MCP-1 TNF-α mice |
| url | https://www.mdpi.com/1422-0067/21/11/3825 |
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