In Vivo Renin Activity Imaging in the Kidney of Progeroid <i>Ercc1</i> Mutant Mice

Changes in the renin–angiotensin system, known for its critical role in the regulation of blood pressure and sodium homeostasis, may contribute to aging and age-related diseases. While the renin–angiotensin system is suppressed during aging, little is known about its regulation and activity within t...

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Autores principales:	Bibi S. van Thiel, Janette van der Linden, Yanto Ridwan, Ingrid M. Garrelds, Marcel Vermeij, Marian C. Clahsen-van Groningen, Fatimunnisa Qadri, Natalia Alenina, Michael Bader, Anton J. M. Roks, A. H. Jan Danser, Jeroen Essers, Ingrid van der Pluijm
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	renin-angiotensin system in vivo imaging renin renal disease renal aging Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/2221e552d1c4466aab4ee29f36edd73a
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spelling	oai:doaj.org-article:2221e552d1c4466aab4ee29f36edd73a2021-11-25T17:56:36ZIn Vivo Renin Activity Imaging in the Kidney of Progeroid <i>Ercc1</i> Mutant Mice10.3390/ijms2222124331422-00671661-6596https://doaj.org/article/2221e552d1c4466aab4ee29f36edd73a2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12433https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Changes in the renin–angiotensin system, known for its critical role in the regulation of blood pressure and sodium homeostasis, may contribute to aging and age-related diseases. While the renin–angiotensin system is suppressed during aging, little is known about its regulation and activity within tissues. However, this knowledge is required to successively treat or prevent renal disease in the elderly. Ercc1 is involved in important DNA repair pathways, and when mutated causes accelerated aging phenotypes in humans and mice. In this study, we hypothesized that unrepaired DNA damage contributes to accelerated kidney failure. We tested the use of the renin-activatable near-infrared fluorescent probe ReninSense680™ in progeroid <i>Ercc1</i><sup><i>d</i>/−</sup> mice and compared renin activity levels in vivo to wild-type mice. First, we validated the specificity of the probe by detecting increased intrarenal activity after losartan treatment and the virtual absence of fluorescence in renin knock-out mice. Second, age-related kidney pathology, tubular anisokaryosis, glomerulosclerosis and increased apoptosis were confirmed in the kidneys of 24-week-old <i>Ercc1</i><sup><i>d</i>/−</sup> mice, while initial renal development was normal. Next, we examined the in vivo renin activity in these <i>Ercc1</i><sup><i>d</i>/−</sup> mice. Interestingly, increased intrarenal renin activity was detected by ReninSense in <i>Ercc1</i><sup><i>d</i>/−</sup> compared to WT mice, while their plasma renin concentrations were lower. Hence, this study demonstrates that intrarenal RAS activity does not necessarily run in parallel with circulating renin in the aging mouse. In addition, our study supports the use of this probe for longitudinal imaging of altered RAS signaling in aging.Bibi S. van ThielJanette van der LindenYanto RidwanIngrid M. GarreldsMarcel VermeijMarian C. Clahsen-van GroningenFatimunnisa QadriNatalia AleninaMichael BaderAnton J. M. RoksA. H. Jan DanserJeroen EssersIngrid van der PluijmMDPI AGarticlerenin-angiotensin systemin vivo imagingreninrenal diseaserenal agingBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12433, p 12433 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	renin-angiotensin system in vivo imaging renin renal disease renal aging Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	renin-angiotensin system in vivo imaging renin renal disease renal aging Biology (General) QH301-705.5 Chemistry QD1-999 Bibi S. van Thiel Janette van der Linden Yanto Ridwan Ingrid M. Garrelds Marcel Vermeij Marian C. Clahsen-van Groningen Fatimunnisa Qadri Natalia Alenina Michael Bader Anton J. M. Roks A. H. Jan Danser Jeroen Essers Ingrid van der Pluijm In Vivo Renin Activity Imaging in the Kidney of Progeroid <i>Ercc1</i> Mutant Mice
description	Changes in the renin–angiotensin system, known for its critical role in the regulation of blood pressure and sodium homeostasis, may contribute to aging and age-related diseases. While the renin–angiotensin system is suppressed during aging, little is known about its regulation and activity within tissues. However, this knowledge is required to successively treat or prevent renal disease in the elderly. Ercc1 is involved in important DNA repair pathways, and when mutated causes accelerated aging phenotypes in humans and mice. In this study, we hypothesized that unrepaired DNA damage contributes to accelerated kidney failure. We tested the use of the renin-activatable near-infrared fluorescent probe ReninSense680™ in progeroid <i>Ercc1</i><sup><i>d</i>/−</sup> mice and compared renin activity levels in vivo to wild-type mice. First, we validated the specificity of the probe by detecting increased intrarenal activity after losartan treatment and the virtual absence of fluorescence in renin knock-out mice. Second, age-related kidney pathology, tubular anisokaryosis, glomerulosclerosis and increased apoptosis were confirmed in the kidneys of 24-week-old <i>Ercc1</i><sup><i>d</i>/−</sup> mice, while initial renal development was normal. Next, we examined the in vivo renin activity in these <i>Ercc1</i><sup><i>d</i>/−</sup> mice. Interestingly, increased intrarenal renin activity was detected by ReninSense in <i>Ercc1</i><sup><i>d</i>/−</sup> compared to WT mice, while their plasma renin concentrations were lower. Hence, this study demonstrates that intrarenal RAS activity does not necessarily run in parallel with circulating renin in the aging mouse. In addition, our study supports the use of this probe for longitudinal imaging of altered RAS signaling in aging.
format	article
author	Bibi S. van Thiel Janette van der Linden Yanto Ridwan Ingrid M. Garrelds Marcel Vermeij Marian C. Clahsen-van Groningen Fatimunnisa Qadri Natalia Alenina Michael Bader Anton J. M. Roks A. H. Jan Danser Jeroen Essers Ingrid van der Pluijm
author_facet	Bibi S. van Thiel Janette van der Linden Yanto Ridwan Ingrid M. Garrelds Marcel Vermeij Marian C. Clahsen-van Groningen Fatimunnisa Qadri Natalia Alenina Michael Bader Anton J. M. Roks A. H. Jan Danser Jeroen Essers Ingrid van der Pluijm
author_sort	Bibi S. van Thiel
title	In Vivo Renin Activity Imaging in the Kidney of Progeroid <i>Ercc1</i> Mutant Mice
title_short	In Vivo Renin Activity Imaging in the Kidney of Progeroid <i>Ercc1</i> Mutant Mice
title_full	In Vivo Renin Activity Imaging in the Kidney of Progeroid <i>Ercc1</i> Mutant Mice
title_fullStr	In Vivo Renin Activity Imaging in the Kidney of Progeroid <i>Ercc1</i> Mutant Mice
title_full_unstemmed	In Vivo Renin Activity Imaging in the Kidney of Progeroid <i>Ercc1</i> Mutant Mice
title_sort	in vivo renin activity imaging in the kidney of progeroid <i>ercc1</i> mutant mice
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/2221e552d1c4466aab4ee29f36edd73a
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In Vivo Renin Activity Imaging in the Kidney of Progeroid <i>Ercc1</i> Mutant Mice

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