ArticleNature medicine2015
PCSK6-mediated corin activation is essential for normal blood pressure.
Article in Nature medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 2 of them syntheses that pooled it.
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Who cites it
74 citing papers in PubMed, 2 syntheses or guidelines pooled it, 141 citations in OpenAlex.
- Genetic and RNA-related molecular markers of trastuzumab-chemotherapy-associated cardiotoxicity in HER2 positive breast cancer: a systematic review.BMC cancer · 2022Pooled it
- A Genome-Wide Association Study of Prediabetes Status Change.Frontiers in endocrinology · 2022Pooled it
- First breed-pool whole genome sequencing of egyptian sheep: a comprehensive genomic atlas revealing diversity and candidate genes for production and adaptation.BMC biotechnology · 2026Article
- Defective Trophoblast Differentiation, Endothelial Dysfunction, and Immune Dysregulation in Preeclampsia Coalesce on a Placental VGLL3-Centered Gene Network.Circulation · 2026Article
- Differential methylation in blood pressure control genes is associated to essential hypertension in African Brazilian populations.Epigenetics · 2025Article
- Beyond Natriuretic Peptides: Corin and Furin As Phenotype-Specific Biomarkers and Therapeutic Gatekeepers in Heart Failure.Current heart failure reports · 2025Review
- Mild Hyperuricemia Attenuates Salt-Sensitive Hypertension and Kidney Damage.Hypertension (Dallas, Tex. : 1979) · 2025Article
- VGLL3-centered network connects placental, vascular, and immune defects in preeclampsia.bioRxiv : the preprint server for biology · 2025Article
- Axl deficiency promotes preeclampsia and vascular malformations in mice.Molecular therapy. Nucleic acids · 2025Article
- Positively charged cytoplasmic residues in corin prevent signal peptidase cleavage and endoplasmic reticulum retention.Communications biology · 2025Article
- Cardiac Localized Polycystin-2 in the Natriuretic Peptide Signaling Pathway and Hypertension.Journal of the American Society of Nephrology : JASN · 2025Article
- Deficiencies in corin and atrial natriuretic peptide-mediated signaling impair endochondral ossification in bone development.Communications biology · 2024Article
- Article
- Functional Roles of Furin in Cardio-Cerebrovascular Diseases.ACS pharmacology & translational science · 2024Review
- Natriuretic Peptide Signaling in Uterine Biology and Preeclampsia.International journal of molecular sciences · 2023Review
- Type II Transmembrane Serine Proteases as Modulators in Adipose Tissue Phenotype and Function.Biomedicines · 2023Review
- PCSK6 and Survival in Idiopathic Pulmonary Fibrosis.American journal of respiratory and critical care medicine · 2023Article
- Bone Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Ameliorated Lipopolysaccharide-Induced Lung Injury Via the miR-21-5p/PCSK6 Pathway.Journal of immunology research · 2023Article
- Corin deficiency impairs cardiac function in mouse models of heart failure.Frontiers in cardiovascular medicine · 2023Article
- Proprotein Convertase Subtilisin/Kexin 6 in Cardiovascular Biology and Disease.International journal of molecular sciences · 2022Review
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
Hypertension is the most common cardiovascular disease, afflicting >30% of adults. The cause of hypertension in most individuals remains unknown, suggesting that additional contributing factors have yet to be discovered. Corin is a serine protease that activates the natriuretic peptides, thereby regulating blood pressure. It is synthesized as a zymogen that is activated by proteolytic cleavage. CORIN variants and mutations impairing corin activation have been identified in people with hypertension and pre-eclampsia. To date, however, the identity of the protease that activates corin remains elusive. Here we show that proprotein convertase subtilisin/kexin-6 (PCSK6, also named PACE4; ref. 10) cleaves and activates corin. In cultured cells, we found that corin activation was inhibited by inhibitors of PCSK family proteases and by small interfering RNAs blocking PCSK6 expression. Conversely, PCSK6 overexpression enhanced corin activation. In addition, purified PCSK6 cleaved wild-type corin but not the R801A variant that lacks the conserved activation site. Pcsk6-knockout mice developed salt-sensitive hypertension, and corin activation and pro-atrial natriuretic peptide processing activity were undetectable in these mice. Moreover, we found that CORIN variants in individuals with hypertension and pre-eclampsia were defective in PCSK6-mediated activation. We also identified a PCSK6 mutation that impaired corin activation activity in a hypertensive patient. Our results indicate that PCSK6 is the long-sought corin activator and is important for sodium homeostasis and normal blood pressure.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.