ArticleThe Journal of clinical investigation2020
Intestinal proinflammatory macrophages induce a phenotypic switch in interstitial cells of Cajal.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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
42 citing papers in PubMed, 50 citations in OpenAlex.
- Phenotypic switching of gastrointestinal smooth muscle cells and the regulatory role of macrophages: a literature review.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Macrophage-enteric nervous system crosstalk in Hirschsprung disease and associated enterocolitis: a focused narrative review with clinical implications.Pediatric surgery international · 2026Review
- Muscularis EGR1 Deficiency Impairs M2 Macrophage Polarization and Disrupts Gastric Motility in Diabetic Gastroparesis.Neurogastroenterology and motility · 2026Article
- Article
- Exosomes derived from M1-macrophage promote enteric neuronal injury via MMP8-TGF-β pathway.Journal of advanced research · 2026Article
- Opioid-Induced Constipation: Mechanistic Insights, Experimental Models, and Future Perspectives.Biomedicines · 2026Review
- Electroacupuncture protects gastric Cajal cells by reducing macrophage pyroptosis in diabetic gastroparesis.World journal of diabetes · 2026Article
- Tight junction dysfunction and cytoskeletal remodeling in Hirschsprung‑associated enterocolitis: A decade of mechanistic insights and therapeutic prospects (Review).Molecular medicine reports · 2026Review
- Review
- Association Between Perioperative Inflammatory Trajectories and Postoperative Hirschsprung-Associated Enterocolitis: Insights from Group-Based Trajectory Modeling.Journal of inflammation research · 2026Article
- Investigating the role of IGF-1 in diabetic gastroparesis: a preliminary review.Acta diabetologica · 2026Review
- IGFBP2 Knockdown Ameliorates Diabetic Gastroparesis by Inhibiting VDAC1-Dependent Mitophagy in Interstitial Cells of CajalEndocrine, metabolic & immune disorders drug targets · 2026Article
- Article
- Hirschsprung's disease may increase the incidence of inflammatory bowel disease through alterations in CA1.Pediatric research · 2025Article
- EMB is essential for enteric nervous system development mediated by PI3K signaling.Genome medicine · 2025Article
- HMGB1 Derived from the Pyroptotic Microenvironment Promotes Macrophage Extracellular Traps in Hirschsprung-Associated Enterocolitis.Advanced biology · 2025Article
- Impairment of stromal-epithelial regenerative cross-talk in Hirschsprung disease primes for the progression to enterocolitis.Science translational medicine · 2025Article
- The Trim32-DPEP2 axis is an inflammatory switch in macrophages during intestinal inflammation.Cell death and differentiation · 2025Article
- A CanineAnimals : an open access journal from MDPI · 2025Article
- Progresses in Questing for the Truth of Opioid-Related Constipation in Cancer Patients.Journal of cellular and molecular medicine · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interstitial cells of Cajal (ICCs) are pacemaker cells in the intestine, and their function can be compromised by loss of C-KIT expression. Macrophage activation has been identified in intestine affected by Hirschsprung disease-associated enterocolitis (HAEC). In this study, we examined proinflammatory macrophage activation and explored the mechanisms by which it downregulates C-KIT expression in ICCs in colon affected by HAEC. We found that macrophage activation and TNF-α production were dramatically increased in the proximal dilated colon of HAEC patients and 3-week-old Ednrb-/- mice. Moreover, ICCs lost their C-KIT+ phenotype in the dilated colon, resulting in damaged pacemaker function and intestinal dysmotility. However, macrophage depletion or TNF-α neutralization led to recovery of ICC phenotype and restored their pacemaker function. In isolated ICCs, TNF-α-mediated phosphorylation of p65 induced overexpression of microRNA-221 (miR-221), resulting in suppression of C-KIT expression and pacemaker currents. We also identified a TNF-α/NF-κB/miR-221 pathway that downregulated C-KIT expression in ICCs in the colon affected by HAEC. These findings suggest the important roles of proinflammatory macrophage activation in a phenotypic switch of ICCs, representing a promising therapeutic target for HAEC.
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.