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

Rosendahl A, Niemann G, Lange S, Ahadzadeh E, Krebs C, Contrepas A, van Goor H, Wiech T, Bader M, Schwake M, Peters J, et al. (2014)
Laboratory Investigation 94(8): 863-872.

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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 C57BI/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.
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Rosendahl A, Niemann G, Lange S, et al. Increased expression of (pro)renin receptor does not cause hypertension or cardiac and renal fibrosis in mice. Laboratory Investigation. 2014;94(8):863-872.
Rosendahl, A., Niemann, G., Lange, S., Ahadzadeh, E., Krebs, C., Contrepas, A., van Goor, H., et al. (2014). Increased expression of (pro)renin receptor does not cause hypertension or cardiac and renal fibrosis in mice. Laboratory Investigation, 94(8), 863-872.
Rosendahl, A., Niemann, G., Lange, S., Ahadzadeh, E., Krebs, C., Contrepas, A., van Goor, H., Wiech, T., Bader, M., Schwake, M., et al. (2014). Increased expression of (pro)renin receptor does not cause hypertension or cardiac and renal fibrosis in mice. Laboratory Investigation 94, 863-872.
Rosendahl, A., et al., 2014. Increased expression of (pro)renin receptor does not cause hypertension or cardiac and renal fibrosis in mice. Laboratory Investigation, 94(8), p 863-872.
A. Rosendahl, et al., “Increased expression of (pro)renin receptor does not cause hypertension or cardiac and renal fibrosis in mice”, Laboratory Investigation, vol. 94, 2014, pp. 863-872.
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.: Increased expression of (pro)renin receptor does not cause hypertension or cardiac and renal fibrosis in mice. Laboratory Investigation. 94, 863-872 (2014).
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, Genevieve, and Wenzel, Ulrich. “Increased expression of (pro)renin receptor does not cause hypertension or cardiac and renal fibrosis in mice”. Laboratory Investigation 94.8 (2014): 863-872.
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