Dataset Information

Delayed Contralateral Nephrectomy Halted Post-Ischemic Renal Fibrosis Progression and Inhibited the Ischemia-Induced Fibromir Upregulation in Mice.

ABSTRACT: (1) Background: Ischemia reperfusion (IR) is the leading cause of acute kidney injury (AKI) and results in predisposition to chronic kidney disease. We demonstrated that delayed contralateral nephrectomy (Nx) greatly improved the function of the IR-injured kidney and decelerated fibrosis progression. Our aim was to identify microRNAs (miRNA/miR) involved in this process. (2) Methods: NMRI mice were subjected to 30 min of renal IR and one week later to Nx/sham surgery. The experiments were conducted for 7-28 days after IR. On day 8, multiplex renal miRNA profiling was performed. Expression of nine miRNAs was determined with qPCR at all time points. Based on the target prediction, plexin-A2 and Cd2AP were measured by Western blot. (3) Results: On day 8 after IR, the expression of 20/1195 miRNAs doubled, and 9/13 selected miRNAs were upregulated at all time points. Nx reduced the expression of several ischemia-induced pro-fibrotic miRNAs (fibromirs), such as miR-142a-duplex, miR-146a-5p, miR-199a-duplex, miR-214-3p and miR-223-3p, in the injured kidneys at various time points. Plexin-A2 was upregulated by IR on day 10, while Cd2AP was unchanged. (4) Conclusion: Nx delayed fibrosis progression and decreased the expression of ischemia-induced fibromirs. The protein expression of plexin-A2 and Cd2AP is mainly regulated by factors other than miRNAs.

SUBMITTER: Roka B

PROVIDER: S-EPMC8301422 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Delayed Contralateral Nephrectomy Halted Post-Ischemic Renal Fibrosis Progression and Inhibited the Ischemia-Induced Fibromir Upregulation in Mice.

Róka Beáta B Tod Pál P Kaucsár Tamás T Bukosza Éva Nóra ÉN Vörös Imre I Varga Zoltán V ZV Petrovich Balázs B Ágg Bence B Ferdinandy Péter P Szénási Gábor G Hamar Péter P

Biomedicines 20210714 7

(1) Background: Ischemia reperfusion (IR) is the leading cause of acute kidney injury (AKI) and results in predisposition to chronic kidney disease. We demonstrated that delayed contralateral nephrectomy (Nx) greatly improved the function of the IR-injured kidney and decelerated fibrosis progression. Our aim was to identify microRNAs (miRNA/miR) involved in this process. (2) Methods: NMRI mice were subjected to 30 min of renal IR and one week later to Nx/sham surgery. The experiments were conduc ...[more]

PMID: 34356879

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Project description:Tubulointerstitial fibrosis is a classic histologic feature of chronic kidney disease (CKD) in cats and a final common pathway toward end-stage renal disease. Domesticated cats have been used in models of ischemia-induced renal fibrosis. The objective of this study was to evaluate the performance of 2 variations of a transient unilateral renal ischemia and delayed contralateral nephrectomy model of tubulointerstitial fibrosis in cats. Purpose-bred, young adult, domesticated cats underwent 90 min of surgically induced ischemia to the right kidney followed by delayed contralateral nephrectomy performed 21 d (RI-CN21d group; n = 10) or 90 d postischemia (RI-CN90d group; n = 12). Control cats underwent sham surgery followed by left nephrectomy 21 d after (sham-CN group; n = 3). Renal functional parameters, including glomerular filtration rate and serum creatinine concentration, were evaluated before and after surgeries. The right kidneys were harvested 120 d postischemia/ sham. Renal histology with lesion scoring and histomorphometry for quantification of smooth muscle actin immunolabeling and collagen staining were performed on harvested kidneys. Severe acute kidney injury prompted euthanasia after left nephrectomy in 5/10 (50.0%), 2/12 (16.7%), and 0/3 (0%) of cats in the RI-CN21d, RI-CN90d, and sham-CN groups, respectively. A significant decrease in glomerular filtration rate by day 120, relative to baseline, occurred in cats in the RI-CN21d group (P < 0.001) and RI-CN90d group (P < 0.001) but not the sham-CN group (P = 0.76). All but one cat in the ischemia groups were azotemic at the study end. Kidneys subjected to ischemia had higher interstitial inflammation, tubular atrophy, and fibrosis scores compared with sham-operated kidneys. There were significant increases in smooth muscle actin immunolabeling and collagen staining in these kidneys, relative to the contralateral kidneys. In summary, 90 min of unilateral renal ischemia and delayed contralateral nephrectomy induced histologic and biochemical changes consistent with CKD in cats. A 90-d period between ischemia and nephrectomy resulted in improved survivability of the model.

Dataset Information

Delayed Contralateral Nephrectomy Halted Post-Ischemic Renal Fibrosis Progression and Inhibited the Ischemia-Induced Fibromir Upregulation in Mice.

Publications

Delayed Contralateral Nephrectomy Halted Post-Ischemic Renal Fibrosis Progression and Inhibited the Ischemia-Induced Fibromir Upregulation in Mice.

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