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MiR-141 mediates recovery from acute kidney injury.

ABSTRACT: Acute kidney injury (AKI) is a global clinical problem characterised by a sudden decline in renal function and mortality as high as 60%. Current AKI biomarkers have limited ability to classify disease progression and identify underlying pathological mechanisms. Here we hypothesised that alterations in urinary microRNA profiles could predict AKI recovery/nonrecovery after 90 days, and that injury-specific changes would signify microRNA mediators of AKI pathology. Comparison of urinary microRNA profiles from AKI patients with controls detected significant injury-specific increases in miR-21, miR-126 and miR-141 (p < 0.05) and decreases in miR-192 (p < 0.001) and miR-204 (p < 0.05). Expression of miR-141 increased in renal proximal tubular epithelial cells (PTECs) under oxidative stress in vitro and unilateral ischaemic reperfusion injury in vivo. Forced miR-141 expression in the presence of H₂O₂ increased PTEC death and decreased cell viability. Of nine messenger RNA targets with two or more miR-141 3'-untranslated region binding sites, we confirmed protein tyrosine phosphatase receptor type G (PTPRG) as a direct miR-141 target in PTECs. PTPRG-specific siRNA knockdown under oxidative stress increased PTEC death and decreased cell viability. In conclusion, we detected significant alterations in five urinary microRNAs following AKI, and identified proximal tubular cell PTPRG as a putative novel therapeutic target.

SUBMITTER: Newbury LJ

PROVIDER: S-EPMC8363617 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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miR-141 mediates recovery from acute kidney injury.

Newbury Lucy J LJ Simpson Kate K Khalid Usman U John Imogen I de Rivera Lluís Bailach LB Lu Yueh-An YA Lopez-Anton Melisa M Watkins William J WJ Jenkins Robert H RH Fraser Donald J DJ Bowen Timothy T

Scientific reports 20210813 1

Acute kidney injury (AKI) is a global clinical problem characterised by a sudden decline in renal function and mortality as high as 60%. Current AKI biomarkers have limited ability to classify disease progression and identify underlying pathological mechanisms. Here we hypothesised that alterations in urinary microRNA profiles could predict AKI recovery/nonrecovery after 90 days, and that injury-specific changes would signify microRNA mediators of AKI pathology. Comparison of urinary microRNA pr ...[more]

PMID: 34389752

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Project description:Background and objectivesAKI requiring dialysis is a contributor to the growing burden of kidney failure, yet little is known about the frequency and patterns of recovery of AKI and its effect on outcomes in patients on incident dialysis.Design, setting, participants, & measurementsUsing the US Renal Data System, we evaluated a cohort of 1,045,540 patients on incident dialysis from January 1, 2005 to December 31, 2014, retrospectively. We examined the association of kidney failure due to AKI with the outcome of all-cause mortality and the associations of sex and race with kidney recovery.ResultsMean age was 63±15 years, and 32,598 (3%) patients on incident dialysis had kidney failure due to AKI. Compared with kidney failure due to diabetes mellitus, kidney failure attributed to AKI was associated with a higher mortality in the first 0-3 months following dialysis initiation (adjusted hazard ratio, 1.28; 95% confidence interval, 1.24 to 1.32) and 3-6 months (adjusted hazard ratio, 1.16; 95% confidence interval, 1.11 to 1.20). Of the patients with kidney failure due to AKI, 11,498 (35%) eventually recovered their kidney function, 95% of those within 12 months. Women had a lower likelihood of kidney recovery than men (adjusted hazard ratio, 0.86; 95% confidence interval, 0.83 to 0.90). Compared with whites, blacks (adjusted hazard ratio, 0.68; 95% confidence interval, 0.64 to 0.72), Asians (adjusted hazard ratio, 0.82; 95% confidence interval, 0.69 to 0.96), Hispanics (adjusted hazard ratio, 0.82; 95% confidence interval, 0.76 to 0.89), and Native Americans (adjusted hazard ratio, 0.72; 95% confidence interval, 0.54 to 0.95) had lower likelihoods of kidney recovery.ConclusionsKidney failure due to AKI confers a higher risk of mortality in the first 6 months compared with kidney failure due to diabetes or other causes. Recovery within 12 months is common, although less so among women than men and among black, Asian, Hispanic, and Native American patients than white patients.

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MiR-141 mediates recovery from acute kidney injury.

Publications

miR-141 mediates recovery from acute kidney injury.

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