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The Interplay between Histamine H4 Receptor and the Kidney Function: The Lesson from H4 Receptor Knockout Mice

Verta, Roberta; Gurrieri, Maura; Borga, Sara; Benetti, Elisa; Pollicino, Paolo; Cavalli, Roberta; Thurmond, Robin L.; Chazot, Paul L.; Pini, Alessandro; Rosa, Arianna Carolina; Grange, Cristina

The Interplay between Histamine H4 Receptor and the Kidney Function: The Lesson from H4 Receptor Knockout Mice Thumbnail


Authors

Roberta Verta

Maura Gurrieri

Sara Borga

Elisa Benetti

Paolo Pollicino

Roberta Cavalli

Robin L. Thurmond

Alessandro Pini

Arianna Carolina Rosa

Cristina Grange



Abstract

Previous studies implicated the histamine H4 receptor in renal pathophysiology. The aim here is to elucidate the role of this receptor on renal function using H4 receptor knockout mice (H4R−/−). Healthy and diabetic H4R−/− mice compared to their C57BL/6J wild-type counterpart for renal function and the expression of crucial tubular proteins. H4R−/− and wild-type mice, matched for ages, showed comparable weight gain curves reaching similar median weight at the end of the study. However, H4R−/− mice displayed a higher basal glycemia. H4R−/− mice showed a lower urine 24 h outflow, and albumin-to-creatinine ratio (ACR) compared to wild-type mice. Consistently, H4R−/− mice presented a higher expression of megalin and a lower basal expression of the sodium-hydrogen exchanger (NHE)3 and aquaporin (AQP)2. According to these basal differences, diabetic H4R−/− mice developed more severe hyperglycemia and a higher 24 h urine volume, but a lower increase in ACR and decrease in urine pH were observed. These events were paralleled by a reduced NHE3 over-expression and megalin loss in diabetic H4R−/− mice. The AQP1 and AQP7 patterns were also different between H4R−/− and wild-type diabetic mice. The collected results highlight the role of the histamine H4 receptor in the control of renal reabsorption processes, particularly albumin uptake.

Citation

Verta, R., Gurrieri, M., Borga, S., Benetti, E., Pollicino, P., Cavalli, R., …Grange, C. (2021). The Interplay between Histamine H4 Receptor and the Kidney Function: The Lesson from H4 Receptor Knockout Mice. Biomolecules, 11(10), https://doi.org/10.3390/biom11101517

Journal Article Type Article
Acceptance Date Oct 13, 2021
Online Publication Date Oct 15, 2021
Publication Date 2021
Deposit Date Jan 25, 2022
Publicly Available Date Mar 29, 2024
Journal Biomolecules
Electronic ISSN 2218-273X
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 11
Issue 10
DOI https://doi.org/10.3390/biom11101517

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Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/

Copyright Statement
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.





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