miR-141 mediates recovery from acute kidney injury

Newbury, Lucy J., Simpson, Kate, Khalid, Usman, John, Imogen, de Rivera, Lluís Bailach, Lu, Yueh-An, Lopez-Anton, Melisa, Watkins, William J. ORCID: https://orcid.org/0000-0003-3262-6588, Jenkins, Robert H. ORCID: https://orcid.org/0000-0001-8500-9044, Fraser, Donald J. ORCID: https://orcid.org/0000-0003-0102-9342 and Bowen, Timothy ORCID: https://orcid.org/0000-0001-6050-0435 2021. miR-141 mediates recovery from acute kidney injury. Scientific Reports 11 (1) , 16499. 10.1038/s41598-021-94984-x

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	Nature Research
ISSN:	2045-2322
Date of First Compliant Deposit:	16 September 2021
Date of Acceptance:	18 June 2021
Last Modified:	25 Aug 2024 01:08
URI:	https://orca.cardiff.ac.uk/id/eprint/144182

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