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Increased expression of (pro)renin receptor does not cause hypertension or cardiac and renal fibrosis in mice

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Increased expression of (pro)renin receptor does not cause hypertension or cardiac and renal fibrosis in mice. / Rosendahl, Alva; Niemann, Gianina; Lange, Sascha; Ahadzadeh, Erfan; Krebs, Christian; Contrepas, Aurelie; van Goor, Harry; Wiech, Thorsten; Bader, Michael; Schwake, Michael; Peters, Judith; Stahl, Rolf; Nguyen, Geneviève; Wenzel, Ulrich O.

In: LAB INVEST, Vol. 94, No. 8, 01.08.2014, p. 863-72.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Rosendahl, A, Niemann, G, Lange, S, Ahadzadeh, E, Krebs, C, Contrepas, A, van Goor, H, Wiech, T, Bader, M, Schwake, M, Peters, J, Stahl, R, Nguyen, G & Wenzel, UO 2014, 'Increased expression of (pro)renin receptor does not cause hypertension or cardiac and renal fibrosis in mice', LAB INVEST, vol. 94, no. 8, pp. 863-72. https://doi.org/10.1038/labinvest.2014.83

APA

Rosendahl, A., Niemann, G., Lange, S., Ahadzadeh, E., Krebs, C., Contrepas, A., van Goor, H., Wiech, T., Bader, M., Schwake, M., Peters, J., Stahl, R., Nguyen, G., & Wenzel, U. O. (2014). Increased expression of (pro)renin receptor does not cause hypertension or cardiac and renal fibrosis in mice. LAB INVEST, 94(8), 863-72. https://doi.org/10.1038/labinvest.2014.83

Vancouver

Rosendahl A, Niemann G, Lange S, Ahadzadeh E, Krebs C, Contrepas A et al. Increased expression of (pro)renin receptor does not cause hypertension or cardiac and renal fibrosis in mice. LAB INVEST. 2014 Aug 1;94(8):863-72. https://doi.org/10.1038/labinvest.2014.83

Bibtex

@article{312c23c325f34290beae085ed7bf2521,
title = "Increased expression of (pro)renin receptor does not cause hypertension or cardiac and renal fibrosis in mice",
abstract = "Binding of renin and prorenin to the (pro)renin receptor (PRR) increases their enzymatic activity and upregulates the expression of pro-fibrotic genes in vitro. Expression of PRR is increased in the heart and kidney of hypertensive and diabetic animals, but its causative role in organ damage is still unclear. To determine whether increased expression of PRR is sufficient to induce cardiac or renal injury, we generated a mouse that constitutively overexpresses PRR by knocking-in the Atp6ap2/PRR gene in the hprt locus under the control of a CMV immediate early enhancer/chicken beta-actin promoter. Mice were backcrossed in the C57Bl/6 and FVB/N strain and studied at the age of 12 months. In spite of a 25- to 80-fold renal and up to 400-fold cardiac increase in Atp6ap2/PRR expression, we found no differences in systolic blood pressure or albuminuria between wild-type and PRR overexpressing littermates. Histological examination did not show any renal or cardiac fibrosis in mutant mice. This was supported by real-time PCR analysis of inflammatory markers as well as of pro-fibrotic genes in the kidney and collagen in cardiac tissue. To determine whether the concomitant increase of renin would trigger fibrosis, we treated PRR overexpressing mice with the angiotensin receptor-1 blocker losartan over a period of 6 weeks. Renin expression increased eightfold in the kidney but no renal injury could be detected. In conclusion, our results suggest no major role for PRR in organ damage per se or related to its function as a receptor of renin.",
keywords = "Albuminuria, Angiotensin II Type 1 Receptor Blockers, Animals, Female, Fibrosis, Heart Ventricles, Hemizygote, Heterozygote, Homozygote, Hypertension, Inflammation Mediators, Kidney, Losartan, Male, Mice, Mice, Inbred Strains, Mice, Transgenic, Proton-Translocating ATPases, Receptors, Cell Surface, Renal Insufficiency, Renin, Up-Regulation, Ventricular Dysfunction",
author = "Alva Rosendahl and Gianina Niemann and Sascha Lange and Erfan Ahadzadeh and Christian Krebs and Aurelie Contrepas and {van Goor}, Harry and Thorsten Wiech and Michael Bader and Michael Schwake and Judith Peters and Rolf Stahl and Genevi{\`e}ve Nguyen and Wenzel, {Ulrich O}",
year = "2014",
month = aug,
day = "1",
doi = "10.1038/labinvest.2014.83",
language = "English",
volume = "94",
pages = "863--72",
journal = "LAB INVEST",
issn = "0023-6837",
publisher = "NATURE PUBLISHING GROUP",
number = "8",

}

RIS

TY - JOUR

T1 - Increased expression of (pro)renin receptor does not cause hypertension or cardiac and renal fibrosis in mice

AU - Rosendahl, Alva

AU - Niemann, Gianina

AU - Lange, Sascha

AU - Ahadzadeh, Erfan

AU - Krebs, Christian

AU - Contrepas, Aurelie

AU - van Goor, Harry

AU - Wiech, Thorsten

AU - Bader, Michael

AU - Schwake, Michael

AU - Peters, Judith

AU - Stahl, Rolf

AU - Nguyen, Geneviève

AU - Wenzel, Ulrich O

PY - 2014/8/1

Y1 - 2014/8/1

N2 - Binding of renin and prorenin to the (pro)renin receptor (PRR) increases their enzymatic activity and upregulates the expression of pro-fibrotic genes in vitro. Expression of PRR is increased in the heart and kidney of hypertensive and diabetic animals, but its causative role in organ damage is still unclear. To determine whether increased expression of PRR is sufficient to induce cardiac or renal injury, we generated a mouse that constitutively overexpresses PRR by knocking-in the Atp6ap2/PRR gene in the hprt locus under the control of a CMV immediate early enhancer/chicken beta-actin promoter. Mice were backcrossed in the C57Bl/6 and FVB/N strain and studied at the age of 12 months. In spite of a 25- to 80-fold renal and up to 400-fold cardiac increase in Atp6ap2/PRR expression, we found no differences in systolic blood pressure or albuminuria between wild-type and PRR overexpressing littermates. Histological examination did not show any renal or cardiac fibrosis in mutant mice. This was supported by real-time PCR analysis of inflammatory markers as well as of pro-fibrotic genes in the kidney and collagen in cardiac tissue. To determine whether the concomitant increase of renin would trigger fibrosis, we treated PRR overexpressing mice with the angiotensin receptor-1 blocker losartan over a period of 6 weeks. Renin expression increased eightfold in the kidney but no renal injury could be detected. In conclusion, our results suggest no major role for PRR in organ damage per se or related to its function as a receptor of renin.

AB - Binding of renin and prorenin to the (pro)renin receptor (PRR) increases their enzymatic activity and upregulates the expression of pro-fibrotic genes in vitro. Expression of PRR is increased in the heart and kidney of hypertensive and diabetic animals, but its causative role in organ damage is still unclear. To determine whether increased expression of PRR is sufficient to induce cardiac or renal injury, we generated a mouse that constitutively overexpresses PRR by knocking-in the Atp6ap2/PRR gene in the hprt locus under the control of a CMV immediate early enhancer/chicken beta-actin promoter. Mice were backcrossed in the C57Bl/6 and FVB/N strain and studied at the age of 12 months. In spite of a 25- to 80-fold renal and up to 400-fold cardiac increase in Atp6ap2/PRR expression, we found no differences in systolic blood pressure or albuminuria between wild-type and PRR overexpressing littermates. Histological examination did not show any renal or cardiac fibrosis in mutant mice. This was supported by real-time PCR analysis of inflammatory markers as well as of pro-fibrotic genes in the kidney and collagen in cardiac tissue. To determine whether the concomitant increase of renin would trigger fibrosis, we treated PRR overexpressing mice with the angiotensin receptor-1 blocker losartan over a period of 6 weeks. Renin expression increased eightfold in the kidney but no renal injury could be detected. In conclusion, our results suggest no major role for PRR in organ damage per se or related to its function as a receptor of renin.

KW - Albuminuria

KW - Angiotensin II Type 1 Receptor Blockers

KW - Animals

KW - Female

KW - Fibrosis

KW - Heart Ventricles

KW - Hemizygote

KW - Heterozygote

KW - Homozygote

KW - Hypertension

KW - Inflammation Mediators

KW - Kidney

KW - Losartan

KW - Male

KW - Mice

KW - Mice, Inbred Strains

KW - Mice, Transgenic

KW - Proton-Translocating ATPases

KW - Receptors, Cell Surface

KW - Renal Insufficiency

KW - Renin

KW - Up-Regulation

KW - Ventricular Dysfunction

U2 - 10.1038/labinvest.2014.83

DO - 10.1038/labinvest.2014.83

M3 - SCORING: Journal article

C2 - 25046440

VL - 94

SP - 863

EP - 872

JO - LAB INVEST

JF - LAB INVEST

SN - 0023-6837

IS - 8

ER -