ArticleFrontiers in cell and developmental biology2019
NLRP2 Regulates Proinflammatory and Antiapoptotic Responses in Proximal Tubular Epithelial Cells.
Article in Frontiers in cell and developmental biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 76 citations in OpenAlex.
- Molecular Evolution of the NLR Gene Family Reveals Diverse Innate Immune Strategies in Bats.Biomolecules · 2025Article
- Atopic dermatitis: diagnosis, molecular pathogenesis, and therapeutics.Molecular biomedicine · 2025Review
- Genome-wide DNA methylation analysis identifies kidney epigenetic dysregulation in a cystinosis mouse model.Frontiers in cell and developmental biology · 2025Article
- Long-read sequencing of hundreds of diverse brains provides insight into the impact of structural variation on gene expression and DNA methylation.bioRxiv : the preprint server for biology · 2024Article
- Ketogenic Diet and Progression of Kidney Disease in Animal Models of Nephropathic Cystinosis.Journal of the American Society of Nephrology : JASN · 2024Article
- The Neglected Sibling: NLRP2 Inflammasome in the Nervous System.Aging and disease · 2024Review
- NLRP inflammasomes in health and disease.Molecular biomedicine · 2024Review
- Lipidomics and Metabolomics in Infant Atopic Dermatitis: What's the Correlation with Early Nutrition?Current pediatric reviews · 2024Review
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- Studies with Human-Induced Pluripotent Stem Cells Reveal That CTNS Mutations Can Alter Renal Proximal Tubule Differentiation.International journal of molecular sciences · 2023Article
- NOD-like Receptor Signaling Pathway in Gastrointestinal Inflammatory Diseases and Cancers.International journal of molecular sciences · 2023Review
- Activation of the NLRP1 Inflammasome and Its Role in Transmissible Gastroenteritis Coronavirus Infection.Journal of virology · 2023Article
- System analysis based on the pyroptosis-related genes identifies GSDMC as a novel therapy target for pancreatic adenocarcinoma.Journal of translational medicine · 2022Article
- Insights into inflammasome regulation: cellular, molecular, and pathogenic control of inflammasome activation.Immunologic research · 2022Review
- Translational Medicine in Uremic Vascular Calcification: Scavenging ROS Attenuates p-Cresyl Sulfate-Activated Caspase-1, NLRP3 Inflammasome and Eicosanoid Inflammation in Human Arterial Smooth Muscle Cells.Life (Basel, Switzerland) · 2022Article
- Programmed Cell Death in Cystinosis.Cells · 2022Review
- Identification of Survival-Specific Genes in Clear Cell Renal Cell Carcinoma Using a Customized Next-Generation Sequencing Gene Panel.Journal of personalized medicine · 2022Article
- Nephropathic Cystinosis: Pathogenic Roles of Inflammation and Potential for New Therapies.Cells · 2022Review
- Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nod-like Receptor Pyrin domain containing proteins (NLRPs) expressed by resident renal cells may contribute to the pathogenesis of multiple renal diseases. Cystinosis is a genetic disorder that affects kidney and particularly proximal tubular epithelial cells (PTEC). Here, we investigated the expression of NLRP family members in human control and cystinotic conditionally immortalized PTEC. Among all the NLRPs tested, we found that NLRP2 is highly expressed in cystinostic PTEC, but not in PTEC from healthy subjects. The NLRP2 overexpression was confirmed in primary PTEC and in kidney biopsies from cystinotic patients. In order to elucidate the role of NLRP2 in PTEC, we stably transfected control PTEC with an NLRP2-containing plasmid. We showed that NLRP2 markedly increases the production of several NF-κB regulated cytokines and chemokines. Accordingly, we demonstrated that NLRP2 interacts with IKKa and positively regulates the DNA-binding activity of p50 and p65 NF-κB, by modulating the p65 NF-κB phosphorylation status in Serine 536. Transcriptome analysis revealed that NLRP2 also upregulates the expression of profibrotic mediators and reduces that of several interferon-inducible genes. Finally, NLRP2 overexpression decreased the apoptotic cell rate. Consistently, silencing of NLRP2 by small-interfering RNA in cystinotic PTEC resulted in a significant decrease in cytokine and chemokine production as well as in an increase in the apoptosis rate. Altogether, our data reveals a previously unrecognized role for NLRP2 in regulating proinflammatory, profibrotic and antiapoptotic responses in PTEC, through NF-κB activation. Moreover, our findings unveil a novel potential mechanism involving NLRP2 overexpression in the pathogenesis of cystinosis.
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