PDLIM2 loss in the epithelium impairs antioxidant responses and adhesion signals preceding the development of ulcerative colitis

Dataset overview

Participants None

Samples 22

Reuse readiness 5.6/10 evidence-backed score

Loss of the PDLIM2 protein during chronic colitis promotes inflammation, impaired epithelium recovery, alterations to the microbiome and oxidative stress.

Ward S, Cox OT, Roggiani S, Crowley T, Turroni S, Melgar S, O'Connor R. · Frontiers in endocrinology · 2026

Abstract

<h4>Introduction</h4>Ulcerative colitis (UC) involves impaired wound healing processes contributing to sustained immune and microbial interactions that aggravate intestinal injury and may progress to colitis-associated cancer (CAC). Here we investigated whether PDLIM2, a known regulator of both epithelial and immune cell fate, contributes to colitis progression.<h4>Methods</h4>PDLIM2 knockout mice (-/-) and wildtype littermates (+/+) were assessed for responses to dextran sodium sulphate (DSS)-induced colitis, and to aoxymethane +DSS. Microbiota were assessed using 16s rRNA amplicon sequencing. Mechanistic studies were carried out in Caco-2 cell cultures, and in silico analysis was carried out on single cell RNA sequencing data from patients with Ulcerative colitis or Crohn's disease.<h4>Results and discussion</h4>Compared to PDLIM2 +/+ mice, PDLIM2 -/- mice exhibited exacerbated and unresolved epithelial damage and inflammation accompanied by immune cell infiltration, which was precluded sufficient time to observe tunour development. PDLIM2 -/- mice exhibited altered basal gut microbial diversity, composition and predicted functionality compared to +/+ mice. Interestingly, in +/+ mice, PDLIM2 expression was lost over the course of DSS-induced colitis. Mechanistic studies in Caco-2 enterocyte cell cultures demonstrated that PDLIM2 suppression resulted in impaired cell adhesion signalling and sustained oxidative stress. In silico analysis of single cell RNA seq data sets from patients with ulcerative colitis and Crohn's disease demonstrated that although PDLIM2 was clearly expressed in normal human colonic epithelial enterocyte populations, its expression declined in both ulcerative colitis and Crohn's disease. We conclude that PDLIM2 is necessary for intestinal homeostasis through regulation of cell adhesion and antioxidant pathways, while loss of PDLIM2 sustains inflammation and epithelial damage.

doi:10.3389/fendo.2025.1720162 ↗ PMID 41743827 ↗ PMC12929155 ↗

Study facts

Organism: —
Platform: Illumina MiSeq
Age group: —
Disease groups: —
Anatomical sites: —

Data availability

Specific data assets have not been resolved from the source yet — see the source repository below for the full file listing.

Strengths & limitations for reuse

Strengths

Raw reads are advertised
Taxonomic tables are advertised
Sample counts are documented

Limitations

Not documented: feature/otu tables are advertised
Not documented: participant counts are documented

Extraction evidence & provenance

Each extracted field is shown with the source excerpt and location used to resolve it.

Assay

Field	Value	Evidence
`assay.paired_end`	True	Sequencing was performed on an Illumina MiSeq platform using a 2 × 250 bp paired-end protocol Section `16S rRNA amplicon sequencing for fecal microbiota profiling`, offset —
`assay.platform`	Illumina MiSeq from source	ENA instrument_model=Illumina MiSeq Section `ENA study report`, offset —
`assay.primers_reported`	True	using the 341F and 785R primers containing Illumina adapter overhang sequences Section `16S rRNA amplicon sequencing for fecal microbiota profiling`, offset —
`assay.read_depth_reported`	345377	yielding 345,377 high-quality reads (mean ± SEM, 15,699 ± 2,546) Section `Results — Loss of PDLIM2 alters gut microbiota composition and functionality`, offset —
`assay.read_length`	250	using a 2 × 250 bp paired-end protocol Section `16S rRNA amplicon sequencing for fecal microbiota profiling`, offset —
`assay.sequencing_type`	amplicon_16s	Samples were processed by 16S rRNA amplicon sequencing Section `Results — Loss of PDLIM2 alters gut microbiota composition and functionality`, offset —
`assay.target_region`	V3–V4	the V3–V4 hypervariable region of the 16S rRNA gene was amplified using the 341F and 785R primers Section `16S rRNA amplicon sequencing for fecal microbiota profiling`, offset —

Cohort

Field Value Evidence

Field	Value	Evidence
`cohort.disease_activity_metadata_available`	True	Daily disease activity index (DDAI) incorporating stool consistency, fur texture, animal posture, and body weight change was assessed Section `Results — PDLIM2 -/- mice are more susceptible to DSS-induced colitis than PDLIM2 +/+ mice`, offset —
`cohort.treatment_exposure_documented`	True	6 for untreated control PDLIM2 +/+ mice, 7 for DSS-treated PDLIM2 +/+, 4 for untreated PDLIM2 -/- and 5 for DSS-treated PDLIM2 -/- Section `Results — Loss of PDLIM2 alters gut microbiota composition and functionality`, offset —
`cohort.treatment_response_metadata_available`	True	PDLIM2 absence and DSS treatment similarly affected the dominant fraction of the microbial ecosystem. Section `Results — Loss of PDLIM2 alters gut microbiota composition and functionality`, offset —

cohort.disease_activity_metadata_available

True

Daily disease activity index (DDAI) incorporating stool consistency, fur texture, animal posture, and body weight change was assessed

Section Results — PDLIM2 -/- mice are more susceptible to DSS-induced colitis than PDLIM2 +/+ mice, offset —

cohort.treatment_exposure_documented

True

6 for untreated control PDLIM2 +/+ mice, 7 for DSS-treated PDLIM2 +/+, 4 for untreated PDLIM2 -/- and 5 for DSS-treated PDLIM2 -/-

Section Results — Loss of PDLIM2 alters gut microbiota composition and functionality, offset —

cohort.treatment_response_metadata_available

True

PDLIM2 absence and DSS treatment similarly affected the dominant fraction of the microbial ecosystem.

Section Results — Loss of PDLIM2 alters gut microbiota composition and functionality, offset —

Data_Assets

Field Value Evidence

Field	Value	Evidence
`data_assets.raw_reads`	True	Sequencing reads were deposited in the National Center for Biotechnology Information Sequence Read Archive (NCBI SRA; BioProject: PRJNA1192040). Section `16S rRNA amplicon sequencing for fecal microbiota profiling`, offset —
`data_assets.taxonomic_table`	True inferred	The latter decreased in PDLIM2 -/- DSS mice compared to PDLIM2 -/- and PDLIM2 +/+ control mice ... Supplementary Table 1 Section `Results — Loss of PDLIM2 alters gut microbiota composition and functionality`, offset —

data_assets.raw_reads

True

Sequencing reads were deposited in the National Center for Biotechnology Information Sequence Read Archive (NCBI SRA; BioProject: PRJNA1192040).

Section 16S rRNA amplicon sequencing for fecal microbiota profiling, offset —

data_assets.taxonomic_table

True inferred

The latter decreased in PDLIM2 -/- DSS mice compared to PDLIM2 -/- and PDLIM2 +/+ control mice ... Supplementary Table 1

Section Results — Loss of PDLIM2 alters gut microbiota composition and functionality, offset —

Specimens

Field	Value	Evidence
`specimens.body_site`	gut	we next compared the gut microbiota profile in these mice to their PDLIM2 +/+ counterparts Section `Results — Loss of PDLIM2 alters gut microbiota composition and functionality`, offset —
`specimens.inflamed_status_available`	True	6 for untreated control PDLIM2 +/+ mice, 7 for DSS-treated PDLIM2 +/+, 4 for untreated PDLIM2 -/- and 5 for DSS-treated PDLIM2 -/- Section `Results — Loss of PDLIM2 alters gut microbiota composition and functionality`, offset —
`specimens.longitudinal_sampling`	False inferred	Stool sampling was performed on the day of culling Section `Results — Loss of PDLIM2 alters gut microbiota composition and functionality`, offset —
`specimens.number_of_samples`	22 from source	ENA sample_count=22 Section `ENA study report`, offset —
`specimens.sample_type`	stool	Stool sampling was performed on the day of culling for a total of 22 samples Section `Results — Loss of PDLIM2 alters gut microbiota composition and functionality`, offset —