ArticleInternational journal of immunopathology and pharmacology
Shikonin improves intestinal barrier function through modulation of GPX4 expression in intestinal epithelial cells.
Article in International journal of immunopathology and pharmacology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Shikonin has been reported to regulate caudal-type homeobox 2 (CDX2)-mediated intestinal epithelial cell (IEC) differentiation, and ferroptosis has been identified a critical event during this process. However, the exact role of ferroptosis in shikonin-induced IEC differentiation remains unclear. Accordingly, the aim of this study was to elucidate the involvement of ferroptosis in CDX2-mediated IEC differentiation induced by shikonin. Real-time polymerase chain reaction, western blotting, luciferase assay, immunoprecipitation, and chromatin immunoprecipitation were used to reveal the mechanism underlying shikonin-modulated ferroptosis-dependent IEC differentiation in HT-29 and Caco-2 cells. Shikonin treatment reduced ferroptosis in IECs, as evidenced by the increased expression of glutathione peroxidase 4 (GPX4) and solute carrier family 7 (cationic amino acid transporter) member 11, which enhanced CDX2 expression and improved IEC barrier function. Mechanistically, shikonin activated the protein kinase A (PKA)/cAMP-responsive element-binding protein (CREB) signaling cascade, promoting CREB binding to the GPX4 promoter and initiating GPX4 transactivation. GPX4 inhibition reversed the effects of shikonin on CDX2 expression. Endogenous pyruvate kinase isozyme M2 interacted with phosphodiesterase 4; this interaction was disrupted by shikonin, leading to the activation of PKA/CREB signaling. The findings of this study indicate that a low dose of shikonin improves IEC barrier function through GPX4-mediated inhibition of ferroptosis, highlighting its potential as a therapeutic agent for intestinal mucosal injury.
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.