Evidence map›Paper›PMID 42902176›Full record

ArticleBMC gastroenterology2026

Epigenetic regulation of INPP5D and its downstream molecular network in autoimmune pancreatitis.

Takeshi Uehara, Mai Iwaya, Shiho Asaka, Tomoyuki Nakajima, Shotaro Komamura, Hiroshi Sawaguchi, Shunsuke Imamura, Akira Nakamura, Shinsuke Sugenoya, Akira Shimizu and 1 more

Abstract read
In one paragraph

Article in BMC gastroenterology, 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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0citing papers 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

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

11 authors.

Takeshi UeharaDepartment of Laboratory Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan. tuehara@shinshu-u.ac.jp.ORCID http://orcid.org/0000-0002-7694-9015
Mai IwayaDepartment of Laboratory Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan.
Shiho AsakaDepartment of Laboratory Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan.
Tomoyuki NakajimaDepartment of Laboratory Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan.
Shotaro KomamuraDepartment of Laboratory Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan.
Hiroshi SawaguchiDepartment of Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan.
Shunsuke ImamuraDepartment of Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan.
Akira NakamuraDepartment of Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan.
Shinsuke SugenoyaDivision of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan.
Akira ShimizuDivision of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan.
Hiroyoshi OtaDepartment of Laboratory Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan.

Funding

Hokuto Foundation for Bioscience noneJSPS KAKENHI JP20K07405
6 · The paper itself

Abstract

aimsAutoimmune pancreatitis (AIP) is a representative manifestation of IgG4-related disease characterized by lymphoplasmacytic inflammation and storiform fibrosis. Although epigenetic dysregulation has been implicated in autoimmune diseases, its contribution to the pathogenesis of AIP remains unclear. METHODS AND

resultsGenome-wide DNA methylation profiling was performed using the Infinium MethylationEPIC array in tissues affected by AIP and obstructive pancreatitis (OP). Differentially methylated regions (DMRs) were identified and subjected to pathway enrichment analysis. Among the significantly enriched gene sets, GNF2_INPP5D showed the strongest enrichment and was selected for further investigation. INPP5D promoter methylation was analyzed, and its protein expression was evaluated by immunohistochemistry. Single-cell RNA sequencing (scRNA-seq) was performed to identify the cells expressing INPP5D. Pathway enrichment analysis showed significant enrichment of the INPP5D-associated immune-regulatory network in AIP. Promoter-associated CpG probes within the INPP5D locus showed predominant hypomethylation in AIP compared with the findings in OP (adjusted p < 0.05). In contrast, immunohistochemistry demonstrated reduced INPP5D expression in spindle-shaped stromal macrophage/histiocyte-lineage cells in AIP tissues. scRNA-seq analysis identified INPP5D expression predominantly in C1QC-positive macrophages and lymphocytes.

conclusionsAIP is characterized by epigenetic remodeling of the INPP5D-associated immune-regulatory network accompanied by reduced INPP5D expression in stromal macrophage-lineage cells. These findings provide evidence for an association between altered INPP5D-related epigenetic regulation and the characteristic fibro-inflammatory microenvironment of AIP. INPP5D may represent a candidate biomarker and a potential therapeutic target in IgG4-related disease.

Indexed as

Autoimmune PancreatitisEpigenesis, GeneticPancreatitisDNA MethylationFemaleHumansMalePromoter Regions, GeneticAutoimmune pancreatitisDNA methylationINPP5DMacrophage

Identifiers

PMID42902176
PMCPMC13685243

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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.