ArticleJournal of nanobiotechnology2025
CREB1/CRTC2 regulated tubular epithelial-derived exosomal miR-93-3p promotes kidney injury induced by calcium oxalate via activating M1 polarization and macrophage extracellular trap formation.
Article in Journal of nanobiotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 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
11 citing papers in PubMed.
- Digoxin Alleviates Osteoarthritis by Inhibiting Macrophage Extracellular Trap Formation via Disruption of the LSP1-SOD1 Interaction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Identification of key molecules and pathways in CaOx crystal-induced renal injury based on metabolomics and proteomics.International urology and nephrology · 2026Article
- Tissue-Resident Macrophage in Inflammation and Cancer.MedComm · 2026Review
- Review
- Cell type-stratified immunogenetic framework reveals immune drivers and therapeutic targets in kidney stone disease.Molecular therapy. Nucleic acids · 2026Article
- Macrophage Extracellular Traps in Immunity and Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Zinc-Containing Bioactive Glass Programs Macrophage Polarization through Extracellular Traps Regulation for Enhanced Diabetic Wound Healing.Advanced healthcare materials · 2026Article
- Advances in understanding exosome-mediated regulation of macrophage function.Frontiers in immunology · 2026Review
- Research progress of exosomes in renal ischemia-reperfusion injury.Frontiers in pharmacology · 2026Review
- Identification of Key Genes Associated with Endoplasmic Reticulum Stress in Calcium Oxalate Kidney Stones.Genes · 2025Article
- Exosomal miR-93-3p targets EIF4EBP1 to regulate macrophage polarization and accelerate wound healing post-anal fistula surgery.Frontiers in pharmacology · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
backgroundCalcium oxalate (CaOx) crystals are known to cause renal injury and trigger inflammatory responses. However, the role of exosome-mediated epithelial-macrophage communication in CaOx-induced kidney injury remains unclear.
methodsTo identify key molecules, miRNA sequencing was conducted on exosomes derived from CaOx-treated (CaOx-exo) and control (Ctrl-exo) epithelial cells, identifying miR-93-3p as significantly upregulated. A combination of dual-luciferase reporter assays, Western blot, RT-qPCR, immunofluorescence staining, flow cytometry, electrophoretic mobility shift assay (EMSA), and chromatin immunoprecipitation-qPCR (CHIP-qPCR) was used to explore the regulation of miR-93-3p by CREB1/CRTC2 and its downstream effects on NFAT5/Akt1/NIK/NF-κB2 signaling in macrophages. The functional roles of NFAT5 in macrophage polarization and macrophage extracellular traps (METs) formation were further evaluated both in vitro and in vivo.
resultsEpithelial exosomes stimulated by CaOx crystals were found to promote kidney injury via macrophage polarization and METs formation. Treatment with NIK SMI1, a NIK inhibitor, or CI-amidine, a METs inhibitor, mitigated crystal deposition and CaOx-induced kidney damage. Overexpression of NFAT5 in a CaOx-induced mouse model reduced renal injury and crystal deposition, downregulated NIK and NF-κB2 levels, and decreased the number of M1-polarized macrophages. Mechanistic studies revealed that miR-93-3p directly targets NFAT5 mRNA, as confirmed by dual-luciferase assays, qRT-PCR, and Western blot. Additionally, we demonstrated that CREB1/CRTC2 acts as a transcriptional activator of miR-93-3p. Inhibition of miR-93-3p partially reversed NIK/NF-κB2 activation and alleviated kidney injury.
conclusionsCaOx crystals exacerbate renal interstitial injury by promoting M1 macrophage polarization and METs formation through the CREB1/CRTC2-exosomal miR-93-3p-NIK/NF-κB2 signaling pathway. Targeting this pathway may provide therapeutic avenues for mitigating crystal deposition-induced kidney 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.