ArticleThe Journal of biological chemistry2015
Exploitation of the Polymeric Immunoglobulin Receptor for Antibody Targeting to Renal Cyst Lumens in Polycystic Kidney Disease.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- EpCAM deficiency causes the inflammation of lungs due to the reduction of pIgR in airway epithelium.Respiratory research · 2026Article
- Development of a cyst-targeted therapy for polycystic kidney disease using an antagonistic dimeric IgA monoclonal antibody against cMET.Cell reports. Medicine · 2025Article
- Inhibiting centrosome clustering reduces cystogenesis and improves kidney function in autosomal dominant polycystic kidney disease.JCI insight · 2024Article
- Review
- STAT signaling in polycystic kidney disease.Cellular signalling · 2020Review
- Comparative proteomic analysis of renal proteins from IgA nephropathy model mice and control mice.Clinical and experimental nephrology · 2020Article
- EfficientFrontiers in chemistry · 2020Article
- IL-4 Receptor α Chain Protects the Kidney Against Tubule-Interstitial Injury Induced by Albumin Overload.Frontiers in physiology · 2020Article
- Emerging targeted strategies for the treatment of autosomal dominant polycystic kidney disease.Clinical kidney journal · 2018Review
- Comparison of folate-conjugated rapamycin versus unconjugated rapamycin in an orthologous mouse model of polycystic kidney disease.American journal of physiology. Renal physiology · 2018Article
- Identification of targets of IL-13 and STAT6 signaling in polycystic kidney disease.American journal of physiology. Renal physiology · 2018Article
- Enhancing IgG distribution to lung mucosal tissue improves protective effect of anti-Pseudomonas aeruginosa antibodies.JCI insight · 2018Article
- A mild reduction of food intake slows disease progression in an orthologous mouse model of polycystic kidney disease.American journal of physiology. Renal physiology · 2016Article
- Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Autosomal-dominant polycystic kidney disease (ADPKD) is a common life-threatening genetic disease that leads to renal failure. No treatment is available yet to effectively slow disease progression. Renal cyst growth is, at least in part, driven by the presence of growth factors in the lumens of renal cysts, which are enclosed spaces lacking connections to the tubular system. We have shown previously shown that IL13 in cyst fluid leads to aberrant activation of STAT6 via the IL4/13 receptor. Although antagonistic antibodies against many of the growth factors implicated in ADPKD are already available, they are IgG isotype antibodies that are not expected to gain access to renal cyst lumens. Here we demonstrate that targeting antibodies to renal cyst lumens is possible with the use of dimeric IgA (dIgA) antibodies. Using human ADPKD tissues and polycystic kidney disease mouse models, we show that the polymeric immunoglobulin receptor (pIgR) is highly expressed by renal cyst-lining cells. pIgR expression is, in part, driven by aberrant STAT6 pathway activation. pIgR actively transports dIgA from the circulation across the cyst epithelium and releases it into the cyst lumen as secretory IgA. dIgA administered by intraperitoneal injection is preferentially targeted to polycystic kidneys whereas injected IgG is not. Our results suggest that pIgR-mediated transcytosis of antagonistic antibodies in dIgA format can be exploited for targeted therapy in ADPKD.
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Registered trials
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