The Protective Role of Natriuretic Peptide Receptor 2 against High Salt Injury in the Renal Papilla

Dugbartey, George J.; Quinn, Breandan; Luo, Liaofu; Mickelsen, Deanne; Ture, Sara; Morrell, Craig N.; Czyzyk, Jan; Doyley, Marvin M.; Yan, Chen; Berk, Bradford C.; Korshunov, Vyacheslav A.

doi:10.1016/j.ajpath.2019.05.020

Cited by 2 publications

(1 citation statement)

References 43 publications

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“…It is also possible that the controversial results regarding NPR-B expression are due to species-dependent differences. Experiments with labeled CNP and immunohistochemical stainings have identified binding sites in renal tissue whose localization is also consistent with our NPR-B in-situ hybridization results [ 16 , 75 ].…”

Section: Discussionsupporting

confidence: 90%

Localization of natriuretic peptide receptors A, B, and C in healthy and diseased mouse kidneys

Heinl

Broeker

Lehrmann

et al. 2022

Pflugers Arch - Eur J Physiol

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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 β positive (PDGFR-β) 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-β 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.

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Section: Discussionsupporting

confidence: 90%

Localization of natriuretic peptide receptors A, B, and C in healthy and diseased mouse kidneys

Heinl

Broeker

Lehrmann

et al. 2022

Pflugers Arch - Eur J Physiol

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Natriuretic Peptide Receptor 2 Locus Contributes to Carotid Remodeling

Korshunov¹,

Smolock²,

Wines-Samuelson³

et al. 2020

JAHA

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Background Carotid artery intima/media thickness ( IMT ) is a hallmark trait associated with future cardiovascular events. The goal of this study was to map new genes that regulate carotid IMT by genome‐wide association. Methods and Results We induced IMT by ligation procedure of the left carotid artery in 30 inbred mouse strains. Histologic reconstruction revealed significant variation in left carotid artery intima, media, adventitia, external elastic lamina volumes, intima‐to‐media ratio, and (intima+media)/ external elastic lamina percent ratio in inbred mice. The carotid remodeling trait was regulated by distinct genomic signatures with a dozen common single‐nucleotide polymorphisms associated with left carotid artery intima volume, intima‐to‐media ratio, and (intima+media)/ external elastic lamina percent ratio. Among genetic loci on mouse chromosomes 1, 4, and 12, there was natriuretic peptide receptor 2 ( Npr2 ), a strong candidate gene. We observed that only male, not female, mice heterozygous for a targeted Npr2 deletion ( Npr2 +/− ) exhibited defective carotid artery remodeling compared with Npr2 wild‐type ( Npr2 +/+ ) littermates. Fibrosis in carotid IMT was significantly increased in Npr2 +/− males compared with Npr2 +/− females or Npr2 +/+ mice. We also detected decreased Npr2 expression in human atherosclerotic plaques, similar to that seen in studies in Npr2 +/− mice. Conclusions We found that components of carotid IMT were regulated by distinct genetic factors. We also showed a critical role for Npr2 in genetic regulation of vascular fibrosis associated with defective carotid remodeling.

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The Protective Role of Natriuretic Peptide Receptor 2 against High Salt Injury in the Renal Papilla

Cited by 2 publications

References 43 publications

Localization of natriuretic peptide receptors A, B, and C in healthy and diseased mouse kidneys

Localization of natriuretic peptide receptors A, B, and C in healthy and diseased mouse kidneys

Natriuretic Peptide Receptor 2 Locus Contributes to Carotid Remodeling

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