ArticleJCI insight2020
Metalloproteinase PAPP-A regulation of IGF-1 contributes to polycystic kidney disease pathogenesis.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- A cross-model single-cell atlas reveals conserved involvement of osteopontin in polycystic kidney disease.JCI insight · 2026Article
- Clinical rather than genetic factors predict hepatic cyst burden and growth in autosomal dominant polycystic kidney disease: a cohort study of 332 genotyped patients.Clinical and experimental nephrology · 2026Article
- Review
- NAT10 inhibition alleviates renal tubular epithelial cell senescence by impeding ac4C acetylation of PAPP-A mRNA in diabetic nephropathy.Cell death & disease · 2026Article
- Contemporary management of advanced chronic kidney disease: An evidence-based review.European journal of internal medicine · 2026Review
- A cross model spatial and single-cell atlas reveals the conserved involvement of osteopontin in polycystic kidney disease.bioRxiv : the preprint server for biology · 2025Article
- The Proteinase PAPP-A has Deep Evolutionary Roots Outside of the IGF System.Genome biology and evolution · 2025Article
- β-hydroxybutyrate recapitulates the beneficial effects of ketogenic metabolic therapy in polycystic kidney disease.iScience · 2024Article
- Identification and Properties of TRPV4 Mutant Channels Present in Polycystic Kidney Disease Patients.Function (Oxford, England) · 2024Article
- Long-Term Effects of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease: Predictors of Treatment Response and Safety over 6 Years of Continuous Therapy.International journal of molecular sciences · 2024Article
- Diet and Physical Activity in Adult Dominant Polycystic Kidney Disease: A Review of the Literature.Nutrients · 2023Review
- Mechanisms of Cyst Development in Polycystic Kidney Disease.Advances in kidney disease and health · 2023Review
- Review of the Use of Animal Models of Human Polycystic Kidney Disease for the Evaluation of Experimental Therapeutic Modalities.Journal of clinical medicine · 2023Review
- Structure of the proteolytic enzyme PAPP-A with the endogenous inhibitor stanniocalcin-2 reveals its inhibitory mechanism.Nature communications · 2022Article
- Pregnancy-associated plasma protein-A (PAPP-A) is a key component of an interactive cellular mechanism promoting pulmonary fibrosis.Journal of cellular physiology · 2022Article
- The genetic background significantly impacts the severity of kidney cystic disease in the Pkd1Kidney international · 2021Article
- A methionine-Mettl3-NCell metabolism · 2021Article
- Inhibition of longevity regulator PAPP-A modulates tissue homeostasis via restraint of mesenchymal stromal cells.Aging cell · 2021Article
- Calcium State-Dependent Regulation of Epithelial Cell Quiescence by Stanniocalcin 1a.Frontiers in cell and developmental biology · 2021Article
- Implications of the PAPP-A-IGFBP-IGF-1 pathway in the pathogenesis and treatment of polycystic kidney disease.Cellular signalling · 2020Review
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of end-stage renal disease (ESRD). The treatment options for ADPKD are limited. We observed an upregulation in several IGF-1 pathway genes in the kidney of Pkd1RC/RC mice, a model of ADPKD. Pregnancy-associated plasma protein A (PAPP-A), a metalloproteinase that cleaves inhibitory IGF binding proteins (IGFBPs), increasing the local bioactivity of IGF-1, was highly induced in the kidney of ADPKD mice. PAPP-A levels were high in cystic fluid and kidneys of humans with ADPKD. Our studies further showed that PAPP-A transcription in ADPKD was mainly regulated through the cAMP/CREB/CBP/p300 pathway. Pappa deficiency effectively inhibited the development of cysts in the Pkd1RC/RC mice. The role of PAPP-A in cystic disease appears to be regulation of the IGF-1 pathway and cellular proliferation in the kidney. Finally, preclinical studies demonstrated that treatment with a monoclonal antibody that blocks the proteolytic activity of PAPP-A against IGFBP4 ameliorated ADPKD cystic disease in vivo in Pkd1RC/RC mice and ex vivo in embryonic kidneys. These data indicated that the PAPP-A/IGF-1 pathway plays an important role in the growth and expansion of cysts in ADPKD. Our findings introduce a therapeutic strategy for ADPKD that involves the inhibition of PAPP-A.
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