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 alt...

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Autores principales:	Lucy J. Newbury, Kate Simpson, Usman Khalid, Imogen John, Lluís Bailach de Rivera, Yueh-An Lu, Melisa Lopez-Anton, William J. Watkins, Robert H. Jenkins, Donald J. Fraser, Timothy Bowen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bbd1249645f6449c9a3ff632580f6632
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spelling	oai:doaj.org-article:bbd1249645f6449c9a3ff632580f66322021-12-02T19:06:44ZmiR-141 mediates recovery from acute kidney injury10.1038/s41598-021-94984-x2045-2322https://doaj.org/article/bbd1249645f6449c9a3ff632580f66322021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94984-xhttps://doaj.org/toc/2045-2322Abstract 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.Lucy J. NewburyKate SimpsonUsman KhalidImogen JohnLluís Bailach de RiveraYueh-An LuMelisa Lopez-AntonWilliam J. WatkinsRobert H. JenkinsDonald J. FraserTimothy BowenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lucy J. Newbury Kate Simpson Usman Khalid Imogen John Lluís Bailach de Rivera Yueh-An Lu Melisa Lopez-Anton William J. Watkins Robert H. Jenkins Donald J. Fraser Timothy Bowen miR-141 mediates recovery from acute kidney injury
description	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.
format	article
author	Lucy J. Newbury Kate Simpson Usman Khalid Imogen John Lluís Bailach de Rivera Yueh-An Lu Melisa Lopez-Anton William J. Watkins Robert H. Jenkins Donald J. Fraser Timothy Bowen
author_facet	Lucy J. Newbury Kate Simpson Usman Khalid Imogen John Lluís Bailach de Rivera Yueh-An Lu Melisa Lopez-Anton William J. Watkins Robert H. Jenkins Donald J. Fraser Timothy Bowen
author_sort	Lucy J. Newbury
title	miR-141 mediates recovery from acute kidney injury
title_short	miR-141 mediates recovery from acute kidney injury
title_full	miR-141 mediates recovery from acute kidney injury
title_fullStr	miR-141 mediates recovery from acute kidney injury
title_full_unstemmed	miR-141 mediates recovery from acute kidney injury
title_sort	mir-141 mediates recovery from acute kidney injury
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/bbd1249645f6449c9a3ff632580f6632
work_keys_str_mv	AT lucyjnewbury mir141mediatesrecoveryfromacutekidneyinjury AT katesimpson mir141mediatesrecoveryfromacutekidneyinjury AT usmankhalid mir141mediatesrecoveryfromacutekidneyinjury AT imogenjohn mir141mediatesrecoveryfromacutekidneyinjury AT lluisbailachderivera mir141mediatesrecoveryfromacutekidneyinjury AT yuehanlu mir141mediatesrecoveryfromacutekidneyinjury AT melisalopezanton mir141mediatesrecoveryfromacutekidneyinjury AT williamjwatkins mir141mediatesrecoveryfromacutekidneyinjury AT roberthjenkins mir141mediatesrecoveryfromacutekidneyinjury AT donaldjfraser mir141mediatesrecoveryfromacutekidneyinjury AT timothybowen mir141mediatesrecoveryfromacutekidneyinjury
_version_	1718377172691845120

miR-141 mediates recovery from acute kidney injury

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