ArticleScientific reports2017
Targeting Neph1 and ZO-1 protein-protein interaction in podocytes prevents podocyte injury and preserves glomerular filtration function.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 26 citations in OpenAlex.
- Article
- Xanthohumol exerts protective function on adriamycin-induced podocyte injury.European journal of nutrition · 2025Article
- Role of the βPharmacological reports : PR · 2024Article
- Modeling Podocyte Ontogeny and Podocytopathies with the Zebrafish.Journal of developmental biology · 2023Review
- Matrix Metalloproteinase-10 in Kidney Injury Repair and Disease.International journal of molecular sciences · 2022Review
- Nanobodies: new avenue to treat kidney disease.Cell and tissue research · 2021Review
- New insight into podocyte slit diaphragm, a therapeutic target of proteinuria.Clinical and experimental nephrology · 2020Review
- Mutations in KIRREL1, a slit diaphragm component, cause steroid-resistant nephrotic syndrome.Kidney international · 2019Article
- Mitochondrial biogenesis induced by the β2-adrenergic receptor agonist formoterol accelerates podocyte recovery from glomerular injury.Kidney international · 2019Article
- Protein phosphatase 2A modulates podocyte maturation and glomerular functional integrity in mice.Cell communication and signaling : CCS · 2019Article
- Disruption of the exocyst induces podocyte loss and dysfunction.The Journal of biological chemistry · 2019Article
- Probing the Druggablility on the Interface of the Protein-Protein Interaction and Its Allosteric Regulation Mechanism on the Drug Screening for the CXCR4 Homodimer.Frontiers in pharmacology · 2019Article
- Nephrin Signaling in the Podocyte: An Updated View of Signal Regulation at the Slit Diaphragm and Beyond.Frontiers in endocrinology · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Targeting protein-protein interaction (PPI) is rapidly becoming an attractive alternative for drug development. While drug development commonly involves inhibiting a PPI, in this study, we show that stabilizing PPI may also be therapeutically beneficial. Junctional proteins Neph1 and ZO-1 and their interaction is an important determinant of the structural integrity of slit diaphragm, which is a critical component of kidney's filtration system. Since injury induces loss of this interaction, we hypothesized that strengthening this interaction may protect kidney's filtration barrier and preserve kidney function. In this study, Neph1-ZO-1 structural complex was screened for the presence of small druggable pockets formed from contributions from both proteins. One such pocket was identified and screened using a small molecule library. Isodesmosine (ISD) a rare naturally occurring amino acid and a biomarker for pulmonary arterial hypertension was selected as the best candidate and to establish the proof of concept, its ability to enhance Neph1-CD and ZO-1 binding was tested. Results from biochemical binding analysis showed that ISD enhanced Neph1 and ZO-1 interaction under in vitro and in vivo conditions. Importantly, ISD treated podocytes were resistant to injury-induced loss of transepithelial permeability. Finally, mouse and zebrafish studies show that ISD protects from injury-induced renal damage.
Indexed as
Identifiers
What OpenQuestion holds
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.