ArticleToxicological sciences : an official journal of the Society of Toxicology2025
Circular RNA hsa_circ_0099188 regulates inducible nitric oxide synthase and chemokine transcription in macrophages by targeting the hsa-miR-381-3p/PPP3CA and hsa-miR-381-3p/KLF4 pathways in response to 4,4'-methylene diphenyl diisocyanate-glutathione conjugate exposure.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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
1 citing paper in PubMed.
- Research progress on circRNAs in type 2 CRS.Frontiers in immunology · 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
3 authors.
Funding
Abstract
Workplace exposure to 4,4'-methylene diphenyl diisocyanate (MDI), the most used monomeric diisocyanate, can lead to the development of occupational asthma (OA). However, the molecular mechanisms by which MDI induces OA remain poorly understood. Previous studies have shown that exposure to MDI or MDI-glutathione (GSH) conjugate reduces the levels of endogenous human (hsa)/murine (mmu)-microRNA (miR)-206/381-3p, triggering the activation of calcineurin/nuclear factor of activated T-cells/inducible nitric oxide synthase (NOS2) regulatory axis and Krüppel-like factor 4 (KLF4)/chemokine pathways in macrophages. Circular RNAs (circRNAs) play important roles on miR and miR-mediated functions in the cells. CircRNA hsa_circ_0008726 is induced by MDI-GSH to downregulate endogenous hsa-miR-206-3p in macrophages; however, the MDI-GSH mediated circRNA response to downregulate hsa-miR-381-3p is currently unknown. The expression of previously identified candidate circRNAs that bind hsa-miR-381-3p were analyzed in differentiated/enhanced THP-1 macrophages treated with MDI-GSH conjugates using RT-qPCR. MDI-GSH exposure induces endogenous hsa_circ_0099188 and its host gene thyrotropin-releasing hormone-degrading ectoenzyme (TRHDE); however, other candidate circRNAs were neither detected nor altered. RNA immunoprecipitation experiments confirmed the binding of hsa-miR-381-3p to hsa_circ_0099188. Further experiments demonstrate that modulating hsa_circ_0099188 expression through siRNAs or overexpression plasmids alter the levels of endogenous hsa-miR-381-3p, PPP3CA, and KLF4, as well as NOS2 and M2 macrophage-associated markers and chemokine transcripts. These findings suggest that MDI/MDI-GSH exposure leads to the downregulation of hsa-miR-381-3p by inducing the expression of hsa_circ_0099188/TRHDE, thereby enhancing the regulatory effects of hsa-miR-381-3p in macrophages.
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.