Evidence map›Paper›PMID 42461884›Full record

ArticlePloS one2026

12-HHT is associated with epithelial barrier enhancement and reduced inflammatory responses in colon organoids of normoganglionosis in Hirschsprung's disease.

Kazuto Suda, Kumpei Abe, Yurina Nishimura, Masafumi Tanaka, Yuki Nagasako, Xuxuan Rao, Jianqin Zhang, Siyi Zeng, Kentaro Fujiwara, Shunsuke Yamada and 4 more

Abstract read
In one paragraph

Article in PloS one, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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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.

2 · The registry

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3 · Its place in the literature

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0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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5 · Who and what money

Authors and funding

14 authors.

Kazuto SudaDepartment of Pediatric General and Urogenital Surgery, Juntendo University School of Medicine, Tokyo, Japan.ORCID https://orcid.org/0000-0001-9136-2039
Kumpei AbeDepartment of Pediatric General and Urogenital Surgery, Juntendo University School of Medicine, Tokyo, Japan.
Yurina NishimuraDepartment of Pediatric General and Urogenital Surgery, Juntendo University School of Medicine, Tokyo, Japan.
Masafumi TanakaDepartment of Pediatric General and Urogenital Surgery, Juntendo University School of Medicine, Tokyo, Japan.
Yuki NagasakoDepartment of Pediatric General and Urogenital Surgery, Juntendo University School of Medicine, Tokyo, Japan.
Xuxuan RaoDepartment of Pediatric General and Urogenital Surgery, Juntendo University School of Medicine, Tokyo, Japan.
Jianqin ZhangDepartment of Pediatric General and Urogenital Surgery, Juntendo University School of Medicine, Tokyo, Japan.
Siyi ZengDepartment of Pediatric General and Urogenital Surgery, Juntendo University School of Medicine, Tokyo, Japan.ORCID https://orcid.org/0009-0003-5167-0821
Kentaro FujiwaraDepartment of Pediatric General and Urogenital Surgery, Juntendo University School of Medicine, Tokyo, Japan.
Shunsuke YamadaDepartment of Pediatric General and Urogenital Surgery, Juntendo University School of Medicine, Tokyo, Japan.
Junya IshiiDepartment of Pediatric General and Urogenital Surgery, Juntendo University School of Medicine, Tokyo, Japan.
Shiho YoshidaDepartment of Pediatric General and Urogenital Surgery, Juntendo University School of Medicine, Tokyo, Japan.
Soichi ShibuyaDepartment of Pediatric General and Urogenital Surgery, Juntendo University School of Medicine, Tokyo, Japan.ORCID https://orcid.org/0000-0002-4274-1312
Go MiyanoDepartment of Pediatric General and Urogenital Surgery, Juntendo University School of Medicine, Tokyo, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeHirschsprung-associated enterocolitis remains a major postoperative complication of Hirschsprung's disease (HD), and impaired epithelial barrier integrity has been proposed as a contributing factor. In this study, we investigated whether 12-hydroxyheptadecatrienoic acid (12-HHT), an endogenous leukotriene B4 receptor 2 (BLT2) agonist, is associated with epithelial barrier enhancement and reduced inflammatory responses in patient-derived colonic organoids.

methodsNormoganglionic specimens from rectal/rectosigmoid HD at pull-through (HD-N; n = 8) and transverse colon specimens from anorectal malformation (ARM) at colostomy closure (n = 10) were used to generate colonic organoids. Epithelia were isolated using ethylenediaminetetraacetic acid and subsequently embedded in Matrigel. Baseline expression of TJP1, TJP2, F11R (encoding junctional adhesion molecule-A), JAM2, CLDN1, CLDN3, CLDN4) and LTB4R2 (encoding BLT2) was assessed by qPCR and immunoblotting. Organoids were then treated with 12-HHT (0.4, 2, or 10 μM) for 7 days, followed by qPCR. Additional experiments assessed cytokine expression (IL1B, IL6) and TJPs after 24 h with tumor necrosis factor-α (TNF-α, 100 ng/mL) plus phosphate buffered saline or 12-HHT. Barrier function was evaluated using FITC-dextran influx assays.

resultsHD-N and ARM organoids exhibited similar growth efficiencies. Baseline expression for F11R, JAM2, CLDN1, CLDN3, CLDN4, and LTB4R2 was significantly lower in HD-N than in ARM. TJPs were upregulated by 12-HHT at 2 and 10 μM in both groups, with stronger effects in ARM. In HD-N organoids, 10 μM 12-HHT suppressed TNF-α-induced IL1B and IL6 elevation mitigated tight junction proteins (TJPs) downregulation more effectively than 2 μM. 12-HHT attenuated TNF-α-induced FITC-dextran influx in HD-N organoids.

conclusion12-HHT is associated with epithelial barrier enhancement and reduced inflammatory responses in HD-N organoids.

Indexed as

ColonHirschsprung DiseaseIntestinal MucosaOrganoidsHumansInflammationIntestinal Barrier FunctionMale

Identifiers

PMID42461884
PMCPMC13374890

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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.