ArticleFrontiers in immunology2025
ATF4 promotes renal tubulointerstitial fibrosis through hexokinase II-mediated glycolysis.
Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 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
2 citing papers in PubMed.
- ATF4: Orchestrating Cellular Stress Adaptation, Metabolism, and Immune Regulation in Health and Disease.International journal of molecular sciences · 2026Review
- Targeting tubular epithelial cell metabolism to halt renal fibrosis: current evidence and future directions.Frontiers in cell and developmental biology · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Renal tubulointerstitial fibrosis is a reliable predictor of progressive chronic kidney disease (CKD). Activating transcription factor 4 (ATF4) has recently emerged as a pivotal player in multiple pathophysiologic processes, particularly the stress response processes. This study aims to explore the role of ATF4 in tubulointerstitial fibrosis from a metabolic perspective. Methods: A murine model of renal fibrosis was generated via unilateral ureteral obstruction (UUO). Quantitative PCR was employed to assess the expression of inflammation-related genes and fibrotic markers in renal tissue, while Western blotting was used to quantify the corresponding protein levels. Immunohistochemistry was performed to determine the localization and expression patterns of ATF4. Lentivirus-mediated ATF4 knockdown mice, along with mice subjected to glycolytic inhibition, were subsequently employed to further investigate their effects on inflammatory mediators and fibrotic markers. In parallel, human renal proximal tubule epithelial cells (HK-2) were exposed to transforming growth factor-β1 (TGF-β1) to induce fibrosis Results: Western blotting and PCR analyses revealed a pronounced elevation of inflammatory cytokines, fibrotic markers, and ATF4 in the renal tissues of UUO mice compared with sham controls. Both Conclusion: In this study, we identified a marked induction of tubular ATF4 in mice subjected to UUO. Silencing ATF4 significantly mitigated renal tubulointerstitial fibrosis. Mechanistically, ATF4 was shown to act as a key glycolytic driver by transcriptionally upregulating hexokinase II. Collectively, these findings indicate that tubular ATF4 facilitates renal tubulointerstitial fibrosis through HK-II mediated glycolytic activation.
Indexed as
Identifiers
What Socratic 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 Socratic graph.