Evidence mapPaperPMID 40839695Full record

ArticlePLoS pathogens2025

DCLK1 isoform (DCLK1-S) as a critical player in promoting inflammation, tissue remodeling, and EMT in mouse models of colitis.

Kafayat Yusuf, Badal C Roy, William L Hauser, Mazin Al-Kasspooles, Sierra Sanchez, Thomas M Attard, Dong Pei, Venkatesh Sampath, Shrikant Anant, Shahid Umar

Abstract read
In one paragraph

Article in PLoS pathogens, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

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.

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

2 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Kafayat YusufDepartment of Surgery, University of Kansas Medical Center, Kansas City, Kansas, United States of America.ORCID https://orcid.org/0000-0003-1258-9193
Badal C RoyDepartment of Surgery, University of Kansas Medical Center, Kansas City, Kansas, United States of America.
William L HauserDepartment of Anesthesiology, University of Kansas Medical Center, Kansas City, Kansas, United States of America.
Mazin Al-KasspoolesDepartment of Surgery, University of Kansas Medical Center, Kansas City, Kansas, United States of America.
Sierra SanchezDepartment of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas, United States of America.
Thomas M AttardDepartment of Pediatric Gastroenterology, Children's Mercy Hospital, Kansas City, Missouri, United States of America.
Dong PeiDepartment of Biostatistics and Data Science, University of Kansas Medical Center, Kansas City, Kansas, United States of America.
Venkatesh SampathDepartment of Pediatrics/Neonatology, Children's Mercy Hospital, Kansas City, Missouri, United States of America.
Shrikant AnantDepartment of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas, United States of America.
Shahid UmarDepartment of Surgery, University of Kansas Medical Center, Kansas City, Kansas, United States of America.ORCID https://orcid.org/0000-0003-0579-6813

Funding

SIGIRR in the Neonatal IntestineR01DK139636 · CHILDREN'S MERCY HOSP (KANSAS CITY, MO) · 2025 to 2025
$631k
NIDDK NIH HHS R01 DK139636
6 · The paper itself

Abstract

BACKGROUND AND

aimsThe Doublecortin-like kinase-1 (DCLK1) plays a chemosensory role in the gut. It's role in the context of inflammatory diseases including inflammatory bowel disease (IBD), has not been thoroughly investigated. This study explored the role of the DCLK1 isoform (DCLK1-S) in promoting infectious/chemical colitis by utilizing high-throughput imaging mass cytometry (IMC).

methodsTransgenic mice were either infected with Citrobacter rodentium (CR) or received DSS and tissues/cells were processed via standard techniques. IMC workflow was adapted by Fluidigm (renamed Standard BioTools). Raw data was fed to Multiplexed Cell Dataset (MCD) Viewer for image generation and analyzed via histoCAT. Promoters for DCLK1 long (DCLK1-L) and short (DCLK1-S) transcripts were cloned, and promoter activities were determined via luciferase reporter assays.

resultsFollowing CR-induced infectious colitis in mice, IMC revealed accumulation of DCLK1-S in the colons of infected mice that inversely correlated with DCLK1-S repressor FoxD3 (Forkhead Box D3). Elevated DCLK1-S levels corresponded with MMP13 staining and activity, promoting collagen degradation and fibrosis. We confirmed the DCLK1-S/MMP13 axis in a knock- in mouse model overexpressing DCLK1-S, in conjunction with dextran sulfate sodium (DSS)- induced colitis. During DCLK1-L and DCLK1-S promoter-reporter assays, we observed a more dramatic decrease in DCLK1-S reporter activity in response to either MMP13 inhibitor, WAY- 170523 or DCLK1 inhibitor, DCLK1-IN-1 compared to the effect of these inhibitors on DCLK1-L promoter. Furthermore, we identified epithelial-to-mesenchymal transition (EMT) as a prelude to colitis.

conclusionsPersistent expression of DCLK1-S drives a severe inflammatory phenotype, contributing to extracellular matrix (ECM) remodeling, fibrosis, and EMT, thus playing pivotal roles in colitis pathogenesis and presenting potential avenues for novel treatment strategies.

Identifiers

PMID40839695
PMCPMC12370143

What Socratic holds

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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 Socratic graph.