ArticlePloS one2009
Ste20-related proline/alanine-rich kinase (SPAK) regulated transcriptionally by hyperosmolarity is involved in intestinal barrier function.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 29 citations in OpenAlex.
- Article
- Article
- Inflammatory hydrocephalus.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2021Article
- SPAK Deficiency Attenuates Chemotherapy-Induced Intestinal Mucositis.Frontiers in oncology · 2021Article
- Cytokine and inflammatory mediator effects on TRPV4 function in choroid plexus epithelial cells.American journal of physiology. Cell physiology · 2019Article
- Hyperosmolar environment and intestinal epithelial cells: impact on mitochondrial oxygen consumption, proliferation, and barrier function in vitro.Scientific reports · 2019Article
- WNK pathways in cancer signaling networks.Cell communication and signaling : CCS · 2018Review
- A miR-34a-Numb Feedforward Loop Triggered by Inflammation Regulates Asymmetric Stem Cell Division in Intestine and Colon Cancer.Cell stem cell · 2016Article
- Rho-A prenylation and signaling link epithelial homeostasis to intestinal inflammation.The Journal of clinical investigation · 2016Article
- Molecular physiology of SPAK and OSR1: two Ste20-related protein kinases regulating ion transport.Physiological reviews · 2012Review
- Overexpression of Ste20-related proline/alanine-rich kinase exacerbates experimental colitis in mice.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
- A novel role for CD46 in wound repair.Frontiers in immunology · 2011Article
- Podocyte injury and albuminuria in mice with podocyte-specific overexpression of the Ste20-like kinase, SLK.The American journal of pathology · 2010Article
- Adenosine 2B receptor expression is post-transcriptionally regulated by microRNA.The Journal of biological chemistry · 2010Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The Ste20-related protein proline/alanine-rich kinase (SPAK) plays important roles in cellular functions such as cell differentiation and regulation of chloride transport, but its roles in pathogenesis of intestinal inflammation remain largely unknown. Here we report significantly increased SPAK expression levels in hyperosmotic environments, such as mucosal biopsy samples from patients with Crohn's disease, as well as colon tissues of C57BL/6 mice and Caco2-BBE cells treated with hyperosmotic medium. NF-kappaB and Sp1-binding sites in the SPAK TATA-less promoter are essential for SPAK mRNA transcription. Hyperosmolarity increases the ability of NF-kappaB and Sp1 to bind to their binding sites. Knock-down of either NF-kappaB or Sp1 by siRNA reduces the hyperosmolarity-induced SPAK expression levels. Furthermore, expression of NF-kappaB, but not Sp1, was upregulated by hyperosmolarity in vivo and in vitro. Nuclear run-on assays showed that hyperosmolarity increases SPAK expression levels at the transcriptional level, without affecting SPAK mRNA stability. Knockdown of SPAK expression by siRNA or overexpression of SPAK in cells and transgenic mice shows that SPAK is involved in intestinal permeability in vitro and in vivo. Together, our data suggest that SPAK, the transcription of which is regulated by hyperosmolarity, plays an important role in epithelial barrier function.
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