Calcium as a second messenger of the action of transforming growth factor-β on insulin secretion

Ishiyama, Nobuyoshi; Shibata, Hiroshi; Kanzaki, Makoto; Shiozaki, Shuichi; Miyazaki, Jun‐ichi; Kobayashi, Isao; Kojima, Itaru

doi:10.1016/0303-7207(95)03726-8

Cited by 23 publications

(12 citation statements)

References 30 publications

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“…It has been reported that TGF-␤1 stimulates Ca 2ϩ influx and mediates an elevation of [Ca 2ϩ ] (27,28), which suggests the possible roles of Ca 2ϩ -dependent events in TGF-␤1-mediated signaling. To study the roles of Ca 2ϩ in TGF-␤1-induced IL-6 expression, the extracellular Ca 2ϩ chelator, EGTA, was used in combined with TGF-␤1.…”

Section: Effects Of Egta On Tgf-␤1-induced Il-6 Expression and Ap-1 Bmentioning

confidence: 98%

“…For example, the TGF-␤1-induced H 2 O 2 generation in HLF cells occurred within 4 -8 h after treatment, peaked at 16 h, and returned to baseline at 48 h (25). Recently, it has been reported that Ca 2ϩ is an intracellular messenger of the action of TGF-␤1 (27,28). TGF-␤1 stimulates Ca 2ϩ influx and mediates an increase in the intracellular Ca 2ϩ concentration [Ca 2ϩ ], which modulates the induction of CTF-1 transcriptional activity in NIH3T3 cells (27).…”

Section: Requirement Of Hydrogen Peroxide Generation In Tgf-␤1 Signalmentioning

confidence: 99%

“…TGF-␤1 stimulates Ca 2ϩ influx and mediates an increase in the intracellular Ca 2ϩ concentration [Ca 2ϩ ], which modulates the induction of CTF-1 transcriptional activity in NIH3T3 cells (27). In MIN6 insulinoma cells, TGF-␤1 elevates the level of [Ca 2ϩ ] which is totally dependent on Ca 2ϩ entry (28). However, the roles of ROS and the relation between ROS and Ca 2ϩ influx in TGF-␤1 signaling are not clear yet.…”

Section: Requirement Of Hydrogen Peroxide Generation In Tgf-␤1 Signalmentioning

confidence: 99%

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Requirement of Hydrogen Peroxide Generation in TGF-β1 Signal Transduction in Human Lung Fibroblast Cells: Involvement of Hydrogen Peroxide and Ca2+ in TGF-β1-Induced IL-6 Expression

Junn

Lee

et al. 2000

The Journal of Immunology

135

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Stimulation of human lung fibroblast cells with TGF-β1 resulted in a transient burst of reactive oxygen species with maximal increase at 5 min after treatment. This reactive oxygen species increase was inhibited by the antioxidant, N-acetyl-l-cysteine (NAC). TGF-β1 treatment stimulated IL-6 gene expression and protein synthesis in human lung fibroblast cells. Antioxidants including NAC, glutathione, and catalase reduced TGF-β1-induced IL-6 gene expression, and direct H2O2 treatment induced IL-6 expression in a dose-dependent manner. NAC also reduced TGF-β1-induced AP-1 binding activity, which is involved in IL-6 gene expression. It has been reported that Ca2+ influx is stimulated by TGF-β1 treatment. EGTA suppressed TGF-β1- or H2O2-induced IL-6 expression, and ionomycin increased IL-6 expression, with simultaneously modulating AP-1 activity in the same pattern. PD98059, an inhibitor of mitogen-activated protein kinase (MAPK) kinase/extracellular signal-related kinase kinase 1, suppressed TGF-β1- or H2O2-induced IL-6 and AP-1 activation. In addition, TGF-β1 or H2O2 increased MAPK activity which was reduced by EGTA and NAC, suggesting that MAPK is involved in TGF-β1-induced IL-6 expression. Taken together, these results indicate that TGF-β1 induces a transient increase of intracellular H2O2 production, which regulates downstream events such as Ca2+ influx, MAPK, and AP-1 activation and IL-6 gene expression.

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Section: Effects Of Egta On Tgf-␤1-induced Il-6 Expression and Ap-1 Bmentioning

confidence: 98%

Section: Requirement Of Hydrogen Peroxide Generation In Tgf-␤1 Signalmentioning

confidence: 99%

Section: Requirement Of Hydrogen Peroxide Generation In Tgf-␤1 Signalmentioning

confidence: 99%

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Requirement of Hydrogen Peroxide Generation in TGF-β1 Signal Transduction in Human Lung Fibroblast Cells: Involvement of Hydrogen Peroxide and Ca2+ in TGF-β1-Induced IL-6 Expression

Junn

Lee

et al. 2000

The Journal of Immunology

135

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“…TGF-␤ has been reported both to increase intracellular calcium (10,11) as well as to inhibit calcium mobilization stimulated by other growth factors (12). Similarly, TGF-␤ has been shown to induce generation of ROS such as superoxide anion and hydrogen peroxide in a variety of cell types (13)(14)(15)(16)(17)(18)(19), and ROS generation is linked to TGF-␤ induction of interleukin-6 gene expression in a signaling pathway that also requires mobilization of calcium (20).…”

Section: Tgf-␤mentioning

confidence: 99%

Involvement of Calcineurin in Transforming Growth Factor-β-mediated Regulation of Extracellular Matrix Accumulation

Gooch

Gorin

Zhang

et al. 2004

Journal of Biological Chemistry

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Calcineurin is a calcium-dependent, serine/threonine phosphatase that functions as a signaling intermediate. In this study, we investigated the role of calcineurin in transforming growth factor-␤ (TGF-␤)-mediated cellular effects and examined the signaling pathway involved in activation of calcineurin. Calcineurin is activated by TGF-␤ in a time-and dose-dependent manner. Consistent with increased phosphatase activity, the calcineurin substrate, NFATc1, is dephosphorylated and transported to the nucleus. Inhibition of calcineurin prior to the addition of TGF-␤ revealed that calcineurin is required for TGF-␤-mediated accumulation of extracellular matrix (ECM) proteins but not cell hypertrophy. Conversely, overexpression of constitutively active calcineurin was sufficient to induce ECM protein expression. The mechanism of calcineurin activation by TGF-␤ was found to be induction of a low, sustained increase of intracellular calcium. Chelation of extracellular calcium blocked both TGF-␤-mediated calcium influx and calcineurin activity. Finally, calcium entry was found to be dependent upon generation of reactive oxygen species (ROS) including superoxide anion and hydrogen peroxide. Accordingly, inhibition of ROS generation also blocked TGF-␤-mediated calcineurin phosphatase activity and decreased ECM accumulation. In conclusion, this study describes a new pathway for TGF-␤-mediated regulation of ECM via generation of ROS, calcium influx, and activation of calcineurin.

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“…Recently, a possible role for calcium in TGF-␤ action has been proposed (7,8). For instance, T␤RI was shown to interact with FKBP12 (9), the prototype of the FKBP class of immunophilins (see Ref.…”

mentioning

confidence: 99%

Regulation of the Transforming Growth Factor β-responsive Transcription Factor CTF-1 by Calcineurin and Calcium/ Calmodulin-dependent Protein Kinase IV

Alevizopoulos

Dusserre

Rüegg

et al. 1997

Journal of Biological Chemistry

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Calcium as a second messenger of the action of transforming growth factor-β on insulin secretion

Cited by 23 publications

References 30 publications

Requirement of Hydrogen Peroxide Generation in TGF-β1 Signal Transduction in Human Lung Fibroblast Cells: Involvement of Hydrogen Peroxide and Ca2+ in TGF-β1-Induced IL-6 Expression

Requirement of Hydrogen Peroxide Generation in TGF-β1 Signal Transduction in Human Lung Fibroblast Cells: Involvement of Hydrogen Peroxide and Ca2+ in TGF-β1-Induced IL-6 Expression

Involvement of Calcineurin in Transforming Growth Factor-β-mediated Regulation of Extracellular Matrix Accumulation

Regulation of the Transforming Growth Factor β-responsive Transcription Factor CTF-1 by Calcineurin and Calcium/ Calmodulin-dependent Protein Kinase IV

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