Heinl, Elena-Sofia and Broeker, Katharina Anna-Elisabeth and Lehrmann, Claudia and Heydn, Rosmarie and Krieger, Katharina and Ortmaier, Katharina and Tauber, Philipp and Schweda, Frank (2023) Localization of natriuretic peptide receptors A, B, and C in healthy and diseased mouse kidneys. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 475 (3). pp. 343-360. ISSN 0031-6768, 1432-2013
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The natriuretic peptides (NPs) ANP (atrial natriuretic peptide) and BNP (B-type natriuretic peptide) mediate their widespread effects by activating the natriuretic peptide receptor-A (NPR-A), while C-type natriuretic peptide (CNP) acts via natriuretic peptide receptor-B (NPR-B). NPs are removed from the circulation by internalization via the natriuretic peptide clearance receptor natriuretic peptide receptor-C (NPR-C). In addition to their well-known functions, for instance on blood pressure, all three NPs confer significant cardioprotection and renoprotection. Since neither the NP-mediated renal functions nor the renal target cells of renoprotection are completely understood, we performed systematic localization studies of NP receptors using in situ hybridization (RNAscope) in mouse kidneys. NPR-A mRNA is highly expressed in glomeruli (mainly podocytes), renal arterioles, endothelial cells of peritubular capillaries, and PDGFR-receptor beta positive (PDGFR-beta) interstitial cells. No NPR-A mRNA was detected by RNAscope in the tubular system. In contrast, NPR-B expression is highest in proximal tubules. NPR-C is located in glomeruli (mainly podocytes), in endothelial cells and PDGFR-beta positive cells. To test for a possible regulation of NPRs in kidney diseases, their distribution was studied in adenine nephropathy. Signal intensity of NPR-A and NPR-B mRNA was reduced while their spatial distribution was unaltered compared with healthy kidneys. In contrast, NPR-C mRNA signal was markedly enhanced in cell clusters of myofibroblasts in fibrotic areas of adenine kidneys. In conclusion, the primary renal targets of ANP and BNP are glomerular, vascular, and interstitial cells but not the tubular compartment, while the CNP receptor NPR-B is highly expressed in proximal tubules. Further studies are needed to clarify the function and interplay of this specific receptor expression pattern.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GUANYLYL CYCLASE-A; GENE-EXPRESSION; MICE LACKING; INJURY; PROLIFERATION; ENDOTHELIUM; PREVENTS; FIBROSIS; CELLS; OVEREXPRESSION; Natriuretic peptide; Natriuretic peptide receptor; Nephroprotection; ANP; BNP; CNP |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Frank Schweda |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Feb 2024 09:42 |
| Last Modified: | 20 Feb 2024 09:42 |
| URI: | https://pred.uni-regensburg.de/id/eprint/56484 |
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