ArticleProceedings of the National Academy of Sciences of the United States of America2007
Substance P mediates antiapoptotic responses in human colonocytes by Akt activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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.
The trial behind it
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Who cites it
49 citing papers in PubMed, 103 citations in OpenAlex.
- Activated notch signaling pathway protects the intestinal barrier in DSS-induced colitis by regulating tight junctions.European journal of medical research · 2026Article
- Neuropeptide SP protects against colitis and linked anxiety-like behavior through the putative roles of gut microbiota and metabolite inositol.Nature communications · 2026Article
- TRPM8 inhibits substance P release from primary sensory neurons via PKA/GSK-3beta to protect colonic epithelium in colitis.Cell death & disease · 2024Article
- Neuropeptide substance P attenuates colitis by suppressing inflammation and ferroptosis via the cGAS-STING signaling pathway.International journal of biological sciences · 2024Article
- The Repurposing of Non-Peptide Neurokinin-1 Receptor Antagonists as Antitumor Drugs: An Urgent Challenge for Aprepitant.International journal of molecular sciences · 2023Review
- Modulating the tachykinin: Role of substance P and neurokinin receptor expression in ocular surface disorders.The ocular surface · 2022Review
- CD4Molecular medicine reports · 2022Article
- ADS024, aFrontiers in microbiology · 2022Article
- Article
- Role of the Neurokinin-1 Receptor in the Promotion of Corneal Epithelial Wound Healing by the Peptides FGLM-NH2 and SSSR in Neurotrophic Keratopathy.Investigative ophthalmology & visual science · 2020Article
- MiR-21 in Substance P-induced exosomes promotes cell proliferation and migration in human colonic epithelial cells.American journal of physiology. Gastrointestinal and liver physiology · 2019Article
- Review
- MicroRNA-31-3p Is Involved in Substance P (SP)-Associated Inflammation in Human Colonic Epithelial Cells and Experimental Colitis.The American journal of pathology · 2018Article
- Role of Corneal Stromal Cells on Epithelial Cell Function during Wound Healing.International journal of molecular sciences · 2018Article
- Substance-P Ameliorates Dextran Sodium Sulfate-Induced Intestinal Damage by Preserving Tissue Barrier Function.Tissue engineering and regenerative medicine · 2018Article
- Role of G protein-coupled receptors-microRNA interactions in gastrointestinal pathophysiology.American journal of physiology. Gastrointestinal and liver physiology · 2017Review
- Sensory neuron regulation of gastrointestinal inflammation and bacterial host defence.Journal of internal medicine · 2017Review
- β-Arrestin 1 has an essential role in neurokinin-1 receptor-mediated glioblastoma cell proliferation and GThe Journal of biological chemistry · 2017Article
- PanIN Neuroendocrine Cells Promote Tumorigenesis via Neuronal Cross-talk.Cancer research · 2017Article
- Effects of alanyl-glutamine supplementation on the small intestinal mucosa barrier in weaned piglets.Asian-Australasian journal of animal sciences · 2017Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
We examined the hypothesis that substance P (SP) and the neurokinin-1 receptor (NK-1R), both in vitro and in vivo, promote mucosal healing during recovery from colitis by stimulating antiapoptotic pathways in human colonic epithelial cells. For the in vitro experiments, human nontransformed NCM460 colonocytes stably transfected with NK-1R (NCM460-NK-1R cells) were exposed to SP, and cell viability assays, TUNEL assays, and Western blot analyses were used to detect apoptotic and antiapoptotic pathways. SP exposure of NCM460-NK-1R colonocytes stimulated phosphorylation of the antiapoptotic molecule Akt and inhibited tamoxifen-induced cell death and apoptosis evaluated by the cell viability assay and poly(ADP-ribose) polymerase cleavage, respectively. SP-induced phosphorylation of Akt and cleavage of poly(ADP-ribose) polymerase were inhibited by blockade of integrin alphaVbeta3, Jak2, and activation of phosphatidylinositol 3-kinase. For the in vivo experiments, C57BL/6 mice, administered 5% dextran sulfate (DSS) dissolved in tap water for 5 days followed by a 5-day recovery period, were treated with the NK-1R antagonist CJ-12,255 or vehicle. Vehicle-treated mice showed increased colonic Akt phosphorylation and apoptosis compared with mice that received no DSS. In contrast, daily i.p. administration of CJ-12,255 for 5 days post-DSS suppressed Akt activation, exacerbated colitis, and enhanced apoptosis, and pharmacologic inhibition of Akt, either alone or together with CJ-12,255, produced a similar effect. Thus, SP, through NK-1R, possesses antiapoptotic effects in the colonic mucosa by activating Akt, which prevents apoptosis and mediates tissue recovery during colitis.
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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.