ArticleThe American journal of pathology2008
Nuclear factor-kappaB is a critical mediator of Ste20-like proline-/alanine-rich kinase regulation in intestinal inflammation.
Article in The American journal of pathology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 47 citations in OpenAlex.
- Target inhibition of SPAK in choroid plexus attenuates T cell infiltration and demyelination in experimental autoimmune encephalomyelitis.Journal of neuroinflammation · 2025Article
- PTEN mutations impair CSF dynamics and cortical networks by dysregulating periventricular neural progenitors.Nature neuroscience · 2025Article
- Evaluation of the Choroid Plexus Epithelium Inflammation TLR4/NF-κB/NKCC1 Signal Pathway Activation in the Development of Hydrocephalus.CNS neuroscience & therapeutics · 2024Article
- SPAK inhibitor ZT-1a attenuates reactive astrogliosis and oligodendrocyte degeneration in a mouse model of vascular dementia.CNS neuroscience & therapeutics · 2024Article
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- Role of SPAK-NKCC1 signaling cascade in the choroid plexus blood-CSF barrier damage after stroke.Journal of neuroinflammation · 2022Article
- WNK1 in Malignant Behaviors: A Potential Target for Cancer?Frontiers in cell and developmental biology · 2022Review
- CpG Single-Site Methylation Regulates TLR2 Expression in Proinflammatory PBMCs From Apical Periodontitis Individuals.Frontiers in immunology · 2022Article
- Macrophages on the margin: choroid plexus immune responses.Trends in neurosciences · 2021Review
- SPAK Deficiency Attenuates Chemotherapy-Induced Intestinal Mucositis.Frontiers in oncology · 2021Article
- Inflammation in acquired hydrocephalus: pathogenic mechanisms and therapeutic targets.Nature reviews. Neurology · 2020Review
- WNK pathways in cancer signaling networks.Cell communication and signaling : CCS · 2018Review
- Paclitaxel Sensitivity of Ovarian Cancer Can be Enhanced by Knocking Down Pairs of Kinases that Regulate MAP4 Phosphorylation and Microtubule Stability.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Pharmacological targeting of SPAK kinase in disorders of impaired epithelial transport.Expert opinion on therapeutic targets · 2017Review
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- Molecular physiology of SPAK and OSR1: two Ste20-related protein kinases regulating ion transport.Physiological reviews · 2012Review
- Tumor necrosis factor alpha modulates the dynamics of the plasminogen-mediated early interaction between Bifidobacterium animalis subsp. lactis and human enterocytes.Applied and environmental microbiology · 2012Article
- RNA splicing is responsive to MBNL1 dose.PloS one · 2012Article
- Overexpression of Ste20-related proline/alanine-rich kinase exacerbates experimental colitis in mice.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Inflammatory bowel disease (IBD) is thought to result from commensal flora, aberrant cellular stress, and genetic factors. Here we show that the expression of colonic Ste20-like proline-/alanine-rich kinase (SPAK) that lacks a PAPA box and an F-alpha helix loop is increased in patients with IBD. The same effects were observed in a mouse model of dextran sodium sulfate-induced colitis and in Caco2-BBE cells treated with the pro-inflammatory cytokine tumor necrosis factor (TNF)-alpha. The 5'-flanking region of the SPAK gene contains two transcriptional start sites, three transcription factor Sp1-binding sites, and one transcription factor nuclear factor (NF)-kappaB-binding site, but no TATA elements. The NF-kappaB-binding site was essential for stimulated SPAK promoter activity by TNF-alpha, whereas the Sp1-binding sites were important for basal promoter activity. siRNA-induced knockdown of NF-kappaB, but not of Sp1, reduced TNF-alpha-induced SPAK expression. Nuclear run-on and mRNA decay assays demonstrated that TNF-alpha directly increased SPAK mRNA transcription without affecting SPAK mRNA stability. Furthermore, up-regulation of NF-kappaB expression and demethylation of the CpG islands induced by TNF-alpha also played roles in the up-regulation of SPAK expression. In conclusion, our data indicate that during inflammatory conditions, TNF-alpha is a key regulator of SPAK expression. The development of compounds that can either modulate or disrupt the activity of SPAK-mediated pathways is therefore important for the control and attenuation of downstream pathological responses, particularly in IBD.
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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.