The Interplay between Histamine H<sub>4</sub> Receptor and the Kidney Function: The Lesson from H<sub>4</sub> Receptor Knockout Mice
Previous studies implicated the histamine H<sub>4</sub> receptor in renal pathophysiology. The aim here is to elucidate the role of this receptor on renal function using H<sub>4</sub> receptor knockout mice (H<sub>4</sub>R<sup>−/−</sup>). Healthy and d...
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| Format: | Article |
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MDPI AG
2021-10-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/11/10/1517 |
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| author | Roberta Verta Maura Gurrieri Sara Borga Elisa Benetti Paolo Pollicino Roberta Cavalli Robin L. Thurmond Paul L. Chazot Alessandro Pini Arianna Carolina Rosa Cristina Grange |
| author_facet | Roberta Verta Maura Gurrieri Sara Borga Elisa Benetti Paolo Pollicino Roberta Cavalli Robin L. Thurmond Paul L. Chazot Alessandro Pini Arianna Carolina Rosa Cristina Grange |
| author_sort | Roberta Verta |
| collection | DOAJ |
| description | Previous studies implicated the histamine H<sub>4</sub> receptor in renal pathophysiology. The aim here is to elucidate the role of this receptor on renal function using H<sub>4</sub> receptor knockout mice (H<sub>4</sub>R<sup>−/−</sup>). Healthy and diabetic H<sub>4</sub>R<sup>−/−</sup> mice compared to their C57BL/6J wild-type counterpart for renal function and the expression of crucial tubular proteins. H<sub>4</sub>R<sup>−/−</sup> and wild-type mice, matched for ages, showed comparable weight gain curves reaching similar median weight at the end of the study. However, H<sub>4</sub>R<sup>−/−</sup> mice displayed a higher basal glycemia. H<sub>4</sub>R<sup>−/−</sup> mice showed a lower urine 24 h outflow, and albumin-to-creatinine ratio (ACR) compared to wild-type mice. Consistently, H<sub>4</sub>R<sup>−/−</sup> 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 H<sub>4</sub>R<sup>−/−</sup> 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 H<sub>4</sub>R<sup>−/−</sup> mice. The AQP1 and AQP7 patterns were also different between H<sub>4</sub>R<sup>−/−</sup> and wild-type diabetic mice. The collected results highlight the role of the histamine H<sub>4</sub> receptor in the control of renal reabsorption processes, particularly albumin uptake. |
| first_indexed | 2024-03-10T06:42:39Z |
| format | Article |
| id | doaj.art-a6762f73aa43475db114f7bdd885f4b0 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T06:42:39Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
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| series | Biomolecules |
| spelling | doaj.art-a6762f73aa43475db114f7bdd885f4b02023-11-22T17:34:52ZengMDPI AGBiomolecules2218-273X2021-10-011110151710.3390/biom11101517The Interplay between Histamine H<sub>4</sub> Receptor and the Kidney Function: The Lesson from H<sub>4</sub> Receptor Knockout MiceRoberta Verta0Maura Gurrieri1Sara Borga2Elisa Benetti3Paolo Pollicino4Roberta Cavalli5Robin L. Thurmond6Paul L. Chazot7Alessandro Pini8Arianna Carolina Rosa9Cristina Grange10Department of Biotechnology and Health Sciences, University of Turin, C.So Dogliotti 14, 10126 Turin, ItalyDepartment of Scienza e Tecnologia del Farmaco, University of Turin, Via P. Giuria 9, 10125 Turin, ItalyDepartment of Scienza e Tecnologia del Farmaco, University of Turin, Via P. Giuria 9, 10125 Turin, ItalyDepartment of Scienza e Tecnologia del Farmaco, University of Turin, Via P. Giuria 9, 10125 Turin, ItalyDirezione Ricerca e Terza Missione, University of Turin, Via Bogino 9 Torino, 10123 Turin, ItalyDepartment of Scienza e Tecnologia del Farmaco, University of Turin, Via P. Giuria 9, 10125 Turin, ItalyJanssen Research & Development, LLC, 3210 Merryfield Row, San Diego, CA 92121, USADepartment of Biosciences and Wolfson Research Institute, Durham University, South Road, Durham DH1 3LE, UKDepartment of Clinical and Experimental Medicine, University of Florence, Viale Pieraccini 6, 50139 Florence, ItalyDepartment of Scienza e Tecnologia del Farmaco, University of Turin, Via P. Giuria 9, 10125 Turin, ItalyDepartment of Medical Sciences, University of Turin, C.So Dogliotti 14, 10126 Turin, ItalyPrevious studies implicated the histamine H<sub>4</sub> receptor in renal pathophysiology. The aim here is to elucidate the role of this receptor on renal function using H<sub>4</sub> receptor knockout mice (H<sub>4</sub>R<sup>−/−</sup>). Healthy and diabetic H<sub>4</sub>R<sup>−/−</sup> mice compared to their C57BL/6J wild-type counterpart for renal function and the expression of crucial tubular proteins. H<sub>4</sub>R<sup>−/−</sup> and wild-type mice, matched for ages, showed comparable weight gain curves reaching similar median weight at the end of the study. However, H<sub>4</sub>R<sup>−/−</sup> mice displayed a higher basal glycemia. H<sub>4</sub>R<sup>−/−</sup> mice showed a lower urine 24 h outflow, and albumin-to-creatinine ratio (ACR) compared to wild-type mice. Consistently, H<sub>4</sub>R<sup>−/−</sup> 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 H<sub>4</sub>R<sup>−/−</sup> 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 H<sub>4</sub>R<sup>−/−</sup> mice. The AQP1 and AQP7 patterns were also different between H<sub>4</sub>R<sup>−/−</sup> and wild-type diabetic mice. The collected results highlight the role of the histamine H<sub>4</sub> receptor in the control of renal reabsorption processes, particularly albumin uptake.https://www.mdpi.com/2218-273X/11/10/1517histamine H<sub>4</sub> receptorsrenal functiondiabetic nephropathy |
| spellingShingle | Roberta Verta Maura Gurrieri Sara Borga Elisa Benetti Paolo Pollicino Roberta Cavalli Robin L. Thurmond Paul L. Chazot Alessandro Pini Arianna Carolina Rosa Cristina Grange The Interplay between Histamine H<sub>4</sub> Receptor and the Kidney Function: The Lesson from H<sub>4</sub> Receptor Knockout Mice Biomolecules histamine H<sub>4</sub> receptors renal function diabetic nephropathy |
| title | The Interplay between Histamine H<sub>4</sub> Receptor and the Kidney Function: The Lesson from H<sub>4</sub> Receptor Knockout Mice |
| title_full | The Interplay between Histamine H<sub>4</sub> Receptor and the Kidney Function: The Lesson from H<sub>4</sub> Receptor Knockout Mice |
| title_fullStr | The Interplay between Histamine H<sub>4</sub> Receptor and the Kidney Function: The Lesson from H<sub>4</sub> Receptor Knockout Mice |
| title_full_unstemmed | The Interplay between Histamine H<sub>4</sub> Receptor and the Kidney Function: The Lesson from H<sub>4</sub> Receptor Knockout Mice |
| title_short | The Interplay between Histamine H<sub>4</sub> Receptor and the Kidney Function: The Lesson from H<sub>4</sub> Receptor Knockout Mice |
| title_sort | interplay between histamine h sub 4 sub receptor and the kidney function the lesson from h sub 4 sub receptor knockout mice |
| topic | histamine H<sub>4</sub> receptors renal function diabetic nephropathy |
| url | https://www.mdpi.com/2218-273X/11/10/1517 |
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