ArticleBiochimica et biophysica acta2015
PAK1 modulates a PPARγ/NF-κB cascade in intestinal inflammation.
Article in Biochimica et biophysica acta, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 46 citations in OpenAlex.
- α‑Cyperone targets the PAK1‑JNK/NF‑κB axis to modulate dendritic cells maturation and Th2/Th9 differentiation in an asthma model.International journal of molecular medicine · 2026Article
- The interplay between p21-activated kinases and tumour-infiltrating dendritic cells and T cells and its implication in pancreatic cancer immunotherapy.Cell communication and signaling : CCS · 2026Review
- The Biological Role of the Signal Transducer and Activator of Transcription 1 (STAT1)-miR-221/222-3p-p21 Activated Kinase 1 (PAK1) Axis in Experimental Periodontitis.Inflammation · 2025Article
- Effect of β-Caryophyllene on PPAR-γ, NF-κB, and CNR2: Implications for Gut-Brain Axis Communication in a Murine Model of Diet-Induced Obesity.Metabolites · 2025Article
- An unexpected tumor-resistant phenotype from floxing PAK1 in a mouse model of colitis associated cancer.Scientific reports · 2025Article
- P21-activated kinase-1 signaling is required to preserve adipose tissue homeostasis and cardiac function.Molecular and cellular biochemistry · 2025Article
- Comprehensive in silico analysis of prognostic and immune infiltrates for FGFs in human ovarian cancer.Journal of ovarian research · 2024Article
- The molecular basis of p21-activated kinase-associated neurodevelopmental disorders: From genotype to phenotype.Frontiers in neuroscience · 2023Review
- The Protective Effects of Iron Free Lactoferrin on Lipopolysaccharide-Induced Intestinal Inflammatory Injury via Modulating the NF-κB/PPAR Signaling Pathway.Foods (Basel, Switzerland) · 2022Article
- Article
- Deletion of P21-activated kinase-1 induces age-dependent increased visceral adiposity and cardiac dysfunction in female mice.Molecular and cellular biochemistry · 2021Article
- Inflammatory Bowel Disease: New Insights into the Interplay between Environmental Factors and PPARγ.International journal of molecular sciences · 2021Review
- PAK1 Silencing Attenuated Proinflammatory Macrophage Activation and Foam Cell Formation by Increasing PPAROxidative medicine and cellular longevity · 2021Article
- A Novel PAK1-Notch1 Axis Regulates Crypt Homeostasis in Intestinal Inflammation.Cellular and molecular gastroenterology and hepatology · 2021Article
- Global hypermethylation of intestinal epithelial cells is a hallmark feature of neonatal surgical necrotizing enterocolitis.Clinical epigenetics · 2020Article
- P21 activated kinase-1 (PAK1) in macrophages is required for promotion of Th17 cell response during helminth infection.Journal of cellular and molecular medicine · 2020Article
- Up-regulation of P21-activated kinase 1 in osteoarthritis chondrocytes is responsible for osteoarthritic cartilage destruction.Bioscience reports · 2020Article
- FGF8 induces therapy resistance in neoadjuvantly radiated rectal cancer.Journal of cancer research and clinical oncology · 2019Article
- 1,8-Cineole Ameliorates LPS-Induced Vascular Endothelium Dysfunction in Mice via PPAR-γ Dependent Regulation of NF-κB.Frontiers in pharmacology · 2019Article
- 5-Aminosalicylic acid downregulates the growth and virulence of Escherichia coli associated with IBD and colorectal cancer, and upregulates host anti-inflammatory activity.The Journal of antibiotics · 2018Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
P21-activated kinases (PAKs) are multifunctional effectors of Rho GTPases with both kinase and scaffolding activity. Here, we investigated the effects of inflammation on PAK1 signaling and its role in colitis-driven carcinogenesis. PAK1 and p-PAK1 (Thr423) were assessed by immunohistochemistry, immunofluorescence, and Western blot. C57BL6/J wildtype mice were treated with a single intraperitoneal TNFα injection. Small intestinal organoids from these mice and from PAK1-KO mice were cultured with TNFα. NF-κB and PPARγ were analyzed upon PAK1 overexpression and silencing for transcriptional/translational regulation. PAK1 expression and activation was increased on the luminal intestinal epithelial surface in inflammatory bowel disease and colitis-associated cancer. PAK1 was phosphorylated upon treatment with IFNγ, IL-1β, and TNFα. In vivo, mice administered with TNFα showed increased p-PAK1 in intestinal villi, which was associated with nuclear p65 and NF-κB activation. p65 nuclear translocation downstream of TNFα was strongly inhibited in PAK1-KO small intestinal organoids. PAK1 overexpression induced a PAK1-p65 interaction as visualized by co-immunoprecipitation, nuclear translocation, and increased NF-κB transactivation, all of which were impeded by kinase-dead PAK1. Moreover, PAK1 overexpression downregulated PPARγ and mesalamine recovered PPARγ through PAK1 inhibition. On the other hand PAK1 silencing inhibited NF-κB, which was recovered using BADGE, a PPARγ antagonist. Altogether these data demonstrate that PAK1 overexpression and activation in inflammation and colitis-associated cancer promote NF-κB activity via suppression of PPARγ in intestinal epithelial cells.
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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.