NFAT5 Induction and Its Role in Hyperosmolar Stressed Human Limbal Epithelial Cells

Lee, Joon‐Hyung; Kim, Min; Im, Young Sun; Choi, Wungrak; Byeon, Suk Ho

doi:10.1167/iovs.07-1142

Cited by 78 publications

(70 citation statements)

References 46 publications

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“…We also generated a mutant in the CRE element known to bind c-Jun (22). Because NF-B is known to be induced by hyperosmotic stress (37,38), we also mutagenized a putative NF-B binding site (Ϫ39 GGGACTTCCG Ϫ30). This putative site was predicted with TFSEARCH and was similar to the NF-B consensus, GGGACTTTCC.…”

Section: Gadd34 Is Induced During Hyperosmotic Stress In An Atf4mentioning

confidence: 99%

Coordinated Regulation of the Neutral Amino Acid Transporter SNAT2 and the Protein Phosphatase Subunit GADD34 Promotes Adaptation to Increased Extracellular Osmolarity

Krokowski

Jobava

Guan

et al. 2015

Journal of Biological Chemistry

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Background: Increased phosphorylation of the translation initiation factor eIF2␣ (eIF2␣-P) promotes apoptosis during hyperosmotic stress. Results: Induction of the PP1 phosphatase subunit GADD34 (which dephosphorylates eIF2␣-P) promotes adaptation. Conclusion: GADD34 promotes survival by increasing the uptake of small neutral amino acids via the amino acid transporter SNAT2. Significance: Rapid adaptation to changes in extracellular osmolarity is inhibited by eIF2␣-P signaling.

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Section: Gadd34 Is Induced During Hyperosmotic Stress In An Atf4mentioning

confidence: 99%

Coordinated Regulation of the Neutral Amino Acid Transporter SNAT2 and the Protein Phosphatase Subunit GADD34 Promotes Adaptation to Increased Extracellular Osmolarity

Krokowski

Jobava

Guan

et al. 2015

Journal of Biological Chemistry

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“…18 In brief, 20 pmol of siRNA was mixed with 1 L of Lipofectamine 2000 (Invitrogen) to form a transduction complex that was then added to a culture medium of low serum concentration. After 4 hours of transduction, the medium was changed to normal medium.…”

Section: Transient Transduction Of Pptk7 or Sirna Directed Against Ptk7mentioning

confidence: 99%

Flt-1 regulates vascular endothelial cell migration via a protein tyrosine kinase-7–dependent pathway

Lee

Chauhan

Kay

et al. 2011

Blood

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“…Pro-inflammatory stimuli, such as TNFα and IL-1β, have been shown to activate NFAT5, 5 offering an important link between NFκB and NFAT5 transcription factor pathways.…”

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confidence: 99%

Activation of osmolyte pathways in inflammatory myopathy and Duchenne muscular dystrophy points to osmoregulation as a contributing pathogenic mechanism

Paepe

Martin

Herbelet

et al. 2016

Laboratory Investigation

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Alongside well-known nuclear factor κB (NFκB) and its associated cytokine networks, nuclear factor of activated T cells 5 (NFAT5), the master regulator of cellular osmoprotective programs, comes forward as an inflammatory regulator. To gain insight into its yet unexplored role in muscle disease, we studied the expression of NFAT5 target proteins involved in osmolyte accumulation: aldose reductase (AR), taurine transporter (TauT), and sodium myo-inositol co-transporter (SMIT). We analyzed idiopathic inflammatory myopathy and Duchenne muscular dystrophy muscle biopsies and myotubes in culture, using immunohistochemistry, immunofluorescence, and western blotting. We report that the level of constitutive AR was upregulated in patients, most strongly so in Duchenne muscular dystrophy. TauT and SMIT expression levels were induced in patients' muscle fibers, mostly representing regenerating and atrophic fibers. In dermatomyositis, strong staining for AR, TauT, and SMIT in atrophic perifascicular fibers was accompanied by staining for other molecular NFAT5 targets, including chaperones, chemokines, and inducible nitric oxide synthase. In these fibers, NFAT5 and NFκB p65 staining coincided, linking both transcription factors with this important pathogenic hallmark. In sporadic inclusion body myositis, SMIT localized to inclusions inside muscle fibers. In addition, SMIT was expressed by a substantial subset of muscle-infiltrating macrophages and T cells in patient biopsies. Our results indicate that osmolyte pathways may contribute to normal muscle functioning, and that activation of AR, TauT, and SMIT in muscle inflammation possibly contributes to the tissue's failing program of damage control.

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NFAT5 Induction and Its Role in Hyperosmolar Stressed Human Limbal Epithelial Cells

Cited by 78 publications

References 46 publications

Coordinated Regulation of the Neutral Amino Acid Transporter SNAT2 and the Protein Phosphatase Subunit GADD34 Promotes Adaptation to Increased Extracellular Osmolarity

Coordinated Regulation of the Neutral Amino Acid Transporter SNAT2 and the Protein Phosphatase Subunit GADD34 Promotes Adaptation to Increased Extracellular Osmolarity

Flt-1 regulates vascular endothelial cell migration via a protein tyrosine kinase-7–dependent pathway

Activation of osmolyte pathways in inflammatory myopathy and Duchenne muscular dystrophy points to osmoregulation as a contributing pathogenic mechanism

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