Publication
Title
Short-term dexamethasone treatment transiently, but not permanently, attenuates fibrosis after acute-to-chronic kidney injury
Author
Abstract
Background Acute kidney injury (AKI) is an underestimated, yet important, risk factor for the development of chronic kidney disease (CKD). Persistence of inflammation after a renal ischemic injury has been observed, both in experimental models and patients, and is thought to be an important mechanisms underlying progression of acute-to-chronic renal injury. Temporary suppression of inflammation immediately after AKI might therefore be a good first-line therapeutic strategy towards a better long term outcome. Methods Male C57Bl/6 J mice (Charles River, 1012 weeks of age) underwent warm (36 °C body temperature) unilateral ischemia-reperfusion of the kidney for 21 min, after which treatment with intraperitoneal injection of the corticosteroid dexamethasone (10 mg/kg) was initiated for 3 weeks. Both at that time point and after an additional 3 week post-treatment follow up period, fibrosis was quantified by collagen I gene expression and immunostaining, as well as gene expression analysis of fibrosis-related genes Tgfβ, Ccn2 (Ctgf), Pai-1 and Ccn3. Furthermore, inflammation was evaluated by Tnfα gene expression and protein expression of the F4/80 macrophage marker and the α-SMA fibroblast marker. Lastly, renal histopathology was quantified by a morphometric analysis of the tubulointerstitial area. Results Treatment with dexamethasone attenuated development of fibrosis, as evidenced by reduced collagen I gene expression and immunostaining, in combination with reduced gene expression of the pro-fibrotic Ccn2 and increased expression of the anti-fibrotic Ccn3. The effects of dexamethasone on renal fibrosis persisted during the 3 week follow up period, as evidenced by stagnation of collagen I deposition in the ischemic kidney, in contrast to vehicle-treatment, where progression of fibrosis was observed. However, expression levels of the pro-fibrotic genes re-approached those of vehicle-treated injured kidneys suggesting that the effects of dexamethasone on fibrosis beyond the treatment period are temporary. Conclusion A short term anti-inflammatory therapy with dexamethasone only transiently attenuates ischemia induced fibrosis. Prolonged or persistent anti-inflammatory treatment seems warranted to achieve long term benefit.
Language
English
Source (journal)
BMC nephrology. - London
Publication
London : 2018
ISSN
1471-2369
Volume/pages
19(2018), 12 p.
Article Reference
343
ISI
000451985700002
Pubmed ID
30509215
Medium
E-only publicatie
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Project info
Overcoming cell cycle arrest in injured kidneys: key to efficient renal regeneration.
Cell cycle control in proximal epithelial cells during progression of acute kidney injury to chronic kidney disease in vivo.
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 12.12.2018
Last edited 15.07.2021
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