Intravital imaging of real-time endogenous actin dysregulation in proximal and distal tubules at the onset of severe ischemia-reperfusion injury

Abstract Severe renal ischemia-reperfusion injury (IRI) can lead to acute and chronic kidney dysfunction. Cytoskeletal modifications are among the main effects of this condition. The majority of studies that have contributed to the current understanding of IRI have relied on histological analyses us...

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Autores principales:	Peter R. Corridon, Shurooq H. Karam, Ali A. Khraibi, Anousha A. Khan, Mohamed A. Alhashmi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1d242833175e47b8b5aa050926f91ffe
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spelling	oai:doaj.org-article:1d242833175e47b8b5aa050926f91ffe2021-12-02T14:27:56ZIntravital imaging of real-time endogenous actin dysregulation in proximal and distal tubules at the onset of severe ischemia-reperfusion injury10.1038/s41598-021-87807-62045-2322https://doaj.org/article/1d242833175e47b8b5aa050926f91ffe2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87807-6https://doaj.org/toc/2045-2322Abstract Severe renal ischemia-reperfusion injury (IRI) can lead to acute and chronic kidney dysfunction. Cytoskeletal modifications are among the main effects of this condition. The majority of studies that have contributed to the current understanding of IRI have relied on histological analyses using exogenous probes after the fact. Here we report the successful real-time visualization of actin cytoskeletal alterations in live proximal and distal tubules that arise at the onset of severe IRI. To achieve this, we induced fluorescent actin expression in these segments in rats with hydrodynamic gene delivery (HGD). Using intravital two-photon microscopy we then tracked and quantified endogenous actin dysregulation that occurred by subjecting these animals to 60 min of bilateral renal ischemia. Rapid (by 1-h post-reperfusion) and significant (up to 50%) declines in actin content were observed. The decline in fluorescence within proximal tubules was significantly greater than that observed in distal tubules. Actin-based fluorescence was not recovered during the measurement period extending 24 h post-reperfusion. Such injury decimated the renal architecture, in particular, actin brush borders, and hampered the reabsorptive and filtrative capacities of these tubular compartments. Thus, for the first time, we show that the combination of HGD and intravital microscopy can serve as an experimental tool to better understand how IRI modifies the cytoskeleton in vivo and provide an extension to current histopathological techniques.Peter R. CorridonShurooq H. KaramAli A. KhraibiAnousha A. KhanMohamed A. AlhashmiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Peter R. Corridon Shurooq H. Karam Ali A. Khraibi Anousha A. Khan Mohamed A. Alhashmi Intravital imaging of real-time endogenous actin dysregulation in proximal and distal tubules at the onset of severe ischemia-reperfusion injury
description	Abstract Severe renal ischemia-reperfusion injury (IRI) can lead to acute and chronic kidney dysfunction. Cytoskeletal modifications are among the main effects of this condition. The majority of studies that have contributed to the current understanding of IRI have relied on histological analyses using exogenous probes after the fact. Here we report the successful real-time visualization of actin cytoskeletal alterations in live proximal and distal tubules that arise at the onset of severe IRI. To achieve this, we induced fluorescent actin expression in these segments in rats with hydrodynamic gene delivery (HGD). Using intravital two-photon microscopy we then tracked and quantified endogenous actin dysregulation that occurred by subjecting these animals to 60 min of bilateral renal ischemia. Rapid (by 1-h post-reperfusion) and significant (up to 50%) declines in actin content were observed. The decline in fluorescence within proximal tubules was significantly greater than that observed in distal tubules. Actin-based fluorescence was not recovered during the measurement period extending 24 h post-reperfusion. Such injury decimated the renal architecture, in particular, actin brush borders, and hampered the reabsorptive and filtrative capacities of these tubular compartments. Thus, for the first time, we show that the combination of HGD and intravital microscopy can serve as an experimental tool to better understand how IRI modifies the cytoskeleton in vivo and provide an extension to current histopathological techniques.
format	article
author	Peter R. Corridon Shurooq H. Karam Ali A. Khraibi Anousha A. Khan Mohamed A. Alhashmi
author_facet	Peter R. Corridon Shurooq H. Karam Ali A. Khraibi Anousha A. Khan Mohamed A. Alhashmi
author_sort	Peter R. Corridon
title	Intravital imaging of real-time endogenous actin dysregulation in proximal and distal tubules at the onset of severe ischemia-reperfusion injury
title_short	Intravital imaging of real-time endogenous actin dysregulation in proximal and distal tubules at the onset of severe ischemia-reperfusion injury
title_full	Intravital imaging of real-time endogenous actin dysregulation in proximal and distal tubules at the onset of severe ischemia-reperfusion injury
title_fullStr	Intravital imaging of real-time endogenous actin dysregulation in proximal and distal tubules at the onset of severe ischemia-reperfusion injury
title_full_unstemmed	Intravital imaging of real-time endogenous actin dysregulation in proximal and distal tubules at the onset of severe ischemia-reperfusion injury
title_sort	intravital imaging of real-time endogenous actin dysregulation in proximal and distal tubules at the onset of severe ischemia-reperfusion injury
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1d242833175e47b8b5aa050926f91ffe
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Intravital imaging of real-time endogenous actin dysregulation in proximal and distal tubules at the onset of severe ischemia-reperfusion injury

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