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Kumar Sharma - One of the best experts on this subject based on the ideXlab platform.

  • role of smad4 on tgf β induced extracellular Matrix Stimulation in mesangial cells
    Kidney International, 2003
    Co-Authors: Ken-ichi Tsuchida, Yanqing Zhu, Senthuran Siva, Stephen R. Dunn, Kumar Sharma
    Abstract:

    Role of Smad4 on TGF-β–induced extracellular Matrix Stimulation in mesangial cells. Background The best characterized signaling pathway employed by transforming growth factor-β (TGF-β) is the Smad pathway; however, its role in Matrix production in mesangial cells is unclear. We focused on Smad4, as Smad4 is essential for the activation of Smad-dependent target genes. Methods To investigate the function of Smad4 in extracellular Matrix (ECM) production, we generated several stably transfected mesangial cell lines (MMC) that have a deletion in the linker region (Smad4ΔM4: Δ275-322) or have a deletion in MH1 of Smad4 (Smad4N4: Δ1-136). The ECM genes, α1 type I collagen (COL1A1), plasminogen activator inhibitor-1 (PAI-1) and fibronectin (FN) were assessed in wild-type mesangial cells and stably transfected Smad4-DN cell lines in the absence and presence of TGF-β. Results As compared to wild-type MMC that had a 10.8-fold Stimulation of TGF-β–induced p3TP-Lux activity, MMC stably transfected with Smad4ΔM4 and Smad4N4 had only a 2.0-fold and 1.3-fold Stimulation, respectively, indicating that they had dominant-negative effects on TGF-β signaling. Basal and TGF-β–induced COL1A1 expression in Smad4 dominant-negative cells were dramatically reduced to very low levels. The early (2 hours) TGF-β–induced PAI-1 mRNA expression was inhibited; however, the sustained (24 to 48 hours) TGF-β–induced expression was not affected in Smad4 dominant-negative cells. For FN, TGF-β–induced expression was maintained in Smad4-dominant negative cells. Conclusion These results indicate that Smad4 is essential for basal and TGF-β–induced COL1A1 expression, and contributes to the early, but not sustained TGF-β–induced PAI-1 expression in mesangial cells. However, TGF-β–induced FN expression is independent of Smad4. In conclusion, Smad4 has a discriminate effect in mediating specific ECM molecules stimulated by TGF-β in mesangial cells.

  • Role of Smad4 on TGF-β–induced extracellular Matrix Stimulation in mesangial cells
    Kidney international, 2003
    Co-Authors: Ken-ichi Tsuchida, Yanqing Zhu, Senthuran Siva, Stephen R. Dunn, Kumar Sharma
    Abstract:

    Role of Smad4 on TGF-β–induced extracellular Matrix Stimulation in mesangial cells. Background The best characterized signaling pathway employed by transforming growth factor-β (TGF-β) is the Smad pathway; however, its role in Matrix production in mesangial cells is unclear. We focused on Smad4, as Smad4 is essential for the activation of Smad-dependent target genes. Methods To investigate the function of Smad4 in extracellular Matrix (ECM) production, we generated several stably transfected mesangial cell lines (MMC) that have a deletion in the linker region (Smad4ΔM4: Δ275-322) or have a deletion in MH1 of Smad4 (Smad4N4: Δ1-136). The ECM genes, α1 type I collagen (COL1A1), plasminogen activator inhibitor-1 (PAI-1) and fibronectin (FN) were assessed in wild-type mesangial cells and stably transfected Smad4-DN cell lines in the absence and presence of TGF-β. Results As compared to wild-type MMC that had a 10.8-fold Stimulation of TGF-β–induced p3TP-Lux activity, MMC stably transfected with Smad4ΔM4 and Smad4N4 had only a 2.0-fold and 1.3-fold Stimulation, respectively, indicating that they had dominant-negative effects on TGF-β signaling. Basal and TGF-β–induced COL1A1 expression in Smad4 dominant-negative cells were dramatically reduced to very low levels. The early (2 hours) TGF-β–induced PAI-1 mRNA expression was inhibited; however, the sustained (24 to 48 hours) TGF-β–induced expression was not affected in Smad4 dominant-negative cells. For FN, TGF-β–induced expression was maintained in Smad4-dominant negative cells. Conclusion These results indicate that Smad4 is essential for basal and TGF-β–induced COL1A1 expression, and contributes to the early, but not sustained TGF-β–induced PAI-1 expression in mesangial cells. However, TGF-β–induced FN expression is independent of Smad4. In conclusion, Smad4 has a discriminate effect in mediating specific ECM molecules stimulated by TGF-β in mesangial cells.

Ken-ichi Tsuchida - One of the best experts on this subject based on the ideXlab platform.

  • role of smad4 on tgf β induced extracellular Matrix Stimulation in mesangial cells
    Kidney International, 2003
    Co-Authors: Ken-ichi Tsuchida, Yanqing Zhu, Senthuran Siva, Stephen R. Dunn, Kumar Sharma
    Abstract:

    Role of Smad4 on TGF-β–induced extracellular Matrix Stimulation in mesangial cells. Background The best characterized signaling pathway employed by transforming growth factor-β (TGF-β) is the Smad pathway; however, its role in Matrix production in mesangial cells is unclear. We focused on Smad4, as Smad4 is essential for the activation of Smad-dependent target genes. Methods To investigate the function of Smad4 in extracellular Matrix (ECM) production, we generated several stably transfected mesangial cell lines (MMC) that have a deletion in the linker region (Smad4ΔM4: Δ275-322) or have a deletion in MH1 of Smad4 (Smad4N4: Δ1-136). The ECM genes, α1 type I collagen (COL1A1), plasminogen activator inhibitor-1 (PAI-1) and fibronectin (FN) were assessed in wild-type mesangial cells and stably transfected Smad4-DN cell lines in the absence and presence of TGF-β. Results As compared to wild-type MMC that had a 10.8-fold Stimulation of TGF-β–induced p3TP-Lux activity, MMC stably transfected with Smad4ΔM4 and Smad4N4 had only a 2.0-fold and 1.3-fold Stimulation, respectively, indicating that they had dominant-negative effects on TGF-β signaling. Basal and TGF-β–induced COL1A1 expression in Smad4 dominant-negative cells were dramatically reduced to very low levels. The early (2 hours) TGF-β–induced PAI-1 mRNA expression was inhibited; however, the sustained (24 to 48 hours) TGF-β–induced expression was not affected in Smad4 dominant-negative cells. For FN, TGF-β–induced expression was maintained in Smad4-dominant negative cells. Conclusion These results indicate that Smad4 is essential for basal and TGF-β–induced COL1A1 expression, and contributes to the early, but not sustained TGF-β–induced PAI-1 expression in mesangial cells. However, TGF-β–induced FN expression is independent of Smad4. In conclusion, Smad4 has a discriminate effect in mediating specific ECM molecules stimulated by TGF-β in mesangial cells.

  • Role of Smad4 on TGF-β–induced extracellular Matrix Stimulation in mesangial cells
    Kidney international, 2003
    Co-Authors: Ken-ichi Tsuchida, Yanqing Zhu, Senthuran Siva, Stephen R. Dunn, Kumar Sharma
    Abstract:

    Role of Smad4 on TGF-β–induced extracellular Matrix Stimulation in mesangial cells. Background The best characterized signaling pathway employed by transforming growth factor-β (TGF-β) is the Smad pathway; however, its role in Matrix production in mesangial cells is unclear. We focused on Smad4, as Smad4 is essential for the activation of Smad-dependent target genes. Methods To investigate the function of Smad4 in extracellular Matrix (ECM) production, we generated several stably transfected mesangial cell lines (MMC) that have a deletion in the linker region (Smad4ΔM4: Δ275-322) or have a deletion in MH1 of Smad4 (Smad4N4: Δ1-136). The ECM genes, α1 type I collagen (COL1A1), plasminogen activator inhibitor-1 (PAI-1) and fibronectin (FN) were assessed in wild-type mesangial cells and stably transfected Smad4-DN cell lines in the absence and presence of TGF-β. Results As compared to wild-type MMC that had a 10.8-fold Stimulation of TGF-β–induced p3TP-Lux activity, MMC stably transfected with Smad4ΔM4 and Smad4N4 had only a 2.0-fold and 1.3-fold Stimulation, respectively, indicating that they had dominant-negative effects on TGF-β signaling. Basal and TGF-β–induced COL1A1 expression in Smad4 dominant-negative cells were dramatically reduced to very low levels. The early (2 hours) TGF-β–induced PAI-1 mRNA expression was inhibited; however, the sustained (24 to 48 hours) TGF-β–induced expression was not affected in Smad4 dominant-negative cells. For FN, TGF-β–induced expression was maintained in Smad4-dominant negative cells. Conclusion These results indicate that Smad4 is essential for basal and TGF-β–induced COL1A1 expression, and contributes to the early, but not sustained TGF-β–induced PAI-1 expression in mesangial cells. However, TGF-β–induced FN expression is independent of Smad4. In conclusion, Smad4 has a discriminate effect in mediating specific ECM molecules stimulated by TGF-β in mesangial cells.

Andre Gerard - One of the best experts on this subject based on the ideXlab platform.

Yanqing Zhu - One of the best experts on this subject based on the ideXlab platform.

  • role of smad4 on tgf β induced extracellular Matrix Stimulation in mesangial cells
    Kidney International, 2003
    Co-Authors: Ken-ichi Tsuchida, Yanqing Zhu, Senthuran Siva, Stephen R. Dunn, Kumar Sharma
    Abstract:

    Role of Smad4 on TGF-β–induced extracellular Matrix Stimulation in mesangial cells. Background The best characterized signaling pathway employed by transforming growth factor-β (TGF-β) is the Smad pathway; however, its role in Matrix production in mesangial cells is unclear. We focused on Smad4, as Smad4 is essential for the activation of Smad-dependent target genes. Methods To investigate the function of Smad4 in extracellular Matrix (ECM) production, we generated several stably transfected mesangial cell lines (MMC) that have a deletion in the linker region (Smad4ΔM4: Δ275-322) or have a deletion in MH1 of Smad4 (Smad4N4: Δ1-136). The ECM genes, α1 type I collagen (COL1A1), plasminogen activator inhibitor-1 (PAI-1) and fibronectin (FN) were assessed in wild-type mesangial cells and stably transfected Smad4-DN cell lines in the absence and presence of TGF-β. Results As compared to wild-type MMC that had a 10.8-fold Stimulation of TGF-β–induced p3TP-Lux activity, MMC stably transfected with Smad4ΔM4 and Smad4N4 had only a 2.0-fold and 1.3-fold Stimulation, respectively, indicating that they had dominant-negative effects on TGF-β signaling. Basal and TGF-β–induced COL1A1 expression in Smad4 dominant-negative cells were dramatically reduced to very low levels. The early (2 hours) TGF-β–induced PAI-1 mRNA expression was inhibited; however, the sustained (24 to 48 hours) TGF-β–induced expression was not affected in Smad4 dominant-negative cells. For FN, TGF-β–induced expression was maintained in Smad4-dominant negative cells. Conclusion These results indicate that Smad4 is essential for basal and TGF-β–induced COL1A1 expression, and contributes to the early, but not sustained TGF-β–induced PAI-1 expression in mesangial cells. However, TGF-β–induced FN expression is independent of Smad4. In conclusion, Smad4 has a discriminate effect in mediating specific ECM molecules stimulated by TGF-β in mesangial cells.

  • Role of Smad4 on TGF-β–induced extracellular Matrix Stimulation in mesangial cells
    Kidney international, 2003
    Co-Authors: Ken-ichi Tsuchida, Yanqing Zhu, Senthuran Siva, Stephen R. Dunn, Kumar Sharma
    Abstract:

    Role of Smad4 on TGF-β–induced extracellular Matrix Stimulation in mesangial cells. Background The best characterized signaling pathway employed by transforming growth factor-β (TGF-β) is the Smad pathway; however, its role in Matrix production in mesangial cells is unclear. We focused on Smad4, as Smad4 is essential for the activation of Smad-dependent target genes. Methods To investigate the function of Smad4 in extracellular Matrix (ECM) production, we generated several stably transfected mesangial cell lines (MMC) that have a deletion in the linker region (Smad4ΔM4: Δ275-322) or have a deletion in MH1 of Smad4 (Smad4N4: Δ1-136). The ECM genes, α1 type I collagen (COL1A1), plasminogen activator inhibitor-1 (PAI-1) and fibronectin (FN) were assessed in wild-type mesangial cells and stably transfected Smad4-DN cell lines in the absence and presence of TGF-β. Results As compared to wild-type MMC that had a 10.8-fold Stimulation of TGF-β–induced p3TP-Lux activity, MMC stably transfected with Smad4ΔM4 and Smad4N4 had only a 2.0-fold and 1.3-fold Stimulation, respectively, indicating that they had dominant-negative effects on TGF-β signaling. Basal and TGF-β–induced COL1A1 expression in Smad4 dominant-negative cells were dramatically reduced to very low levels. The early (2 hours) TGF-β–induced PAI-1 mRNA expression was inhibited; however, the sustained (24 to 48 hours) TGF-β–induced expression was not affected in Smad4 dominant-negative cells. For FN, TGF-β–induced expression was maintained in Smad4-dominant negative cells. Conclusion These results indicate that Smad4 is essential for basal and TGF-β–induced COL1A1 expression, and contributes to the early, but not sustained TGF-β–induced PAI-1 expression in mesangial cells. However, TGF-β–induced FN expression is independent of Smad4. In conclusion, Smad4 has a discriminate effect in mediating specific ECM molecules stimulated by TGF-β in mesangial cells.

Senthuran Siva - One of the best experts on this subject based on the ideXlab platform.

  • role of smad4 on tgf β induced extracellular Matrix Stimulation in mesangial cells
    Kidney International, 2003
    Co-Authors: Ken-ichi Tsuchida, Yanqing Zhu, Senthuran Siva, Stephen R. Dunn, Kumar Sharma
    Abstract:

    Role of Smad4 on TGF-β–induced extracellular Matrix Stimulation in mesangial cells. Background The best characterized signaling pathway employed by transforming growth factor-β (TGF-β) is the Smad pathway; however, its role in Matrix production in mesangial cells is unclear. We focused on Smad4, as Smad4 is essential for the activation of Smad-dependent target genes. Methods To investigate the function of Smad4 in extracellular Matrix (ECM) production, we generated several stably transfected mesangial cell lines (MMC) that have a deletion in the linker region (Smad4ΔM4: Δ275-322) or have a deletion in MH1 of Smad4 (Smad4N4: Δ1-136). The ECM genes, α1 type I collagen (COL1A1), plasminogen activator inhibitor-1 (PAI-1) and fibronectin (FN) were assessed in wild-type mesangial cells and stably transfected Smad4-DN cell lines in the absence and presence of TGF-β. Results As compared to wild-type MMC that had a 10.8-fold Stimulation of TGF-β–induced p3TP-Lux activity, MMC stably transfected with Smad4ΔM4 and Smad4N4 had only a 2.0-fold and 1.3-fold Stimulation, respectively, indicating that they had dominant-negative effects on TGF-β signaling. Basal and TGF-β–induced COL1A1 expression in Smad4 dominant-negative cells were dramatically reduced to very low levels. The early (2 hours) TGF-β–induced PAI-1 mRNA expression was inhibited; however, the sustained (24 to 48 hours) TGF-β–induced expression was not affected in Smad4 dominant-negative cells. For FN, TGF-β–induced expression was maintained in Smad4-dominant negative cells. Conclusion These results indicate that Smad4 is essential for basal and TGF-β–induced COL1A1 expression, and contributes to the early, but not sustained TGF-β–induced PAI-1 expression in mesangial cells. However, TGF-β–induced FN expression is independent of Smad4. In conclusion, Smad4 has a discriminate effect in mediating specific ECM molecules stimulated by TGF-β in mesangial cells.

  • Role of Smad4 on TGF-β–induced extracellular Matrix Stimulation in mesangial cells
    Kidney international, 2003
    Co-Authors: Ken-ichi Tsuchida, Yanqing Zhu, Senthuran Siva, Stephen R. Dunn, Kumar Sharma
    Abstract:

    Role of Smad4 on TGF-β–induced extracellular Matrix Stimulation in mesangial cells. Background The best characterized signaling pathway employed by transforming growth factor-β (TGF-β) is the Smad pathway; however, its role in Matrix production in mesangial cells is unclear. We focused on Smad4, as Smad4 is essential for the activation of Smad-dependent target genes. Methods To investigate the function of Smad4 in extracellular Matrix (ECM) production, we generated several stably transfected mesangial cell lines (MMC) that have a deletion in the linker region (Smad4ΔM4: Δ275-322) or have a deletion in MH1 of Smad4 (Smad4N4: Δ1-136). The ECM genes, α1 type I collagen (COL1A1), plasminogen activator inhibitor-1 (PAI-1) and fibronectin (FN) were assessed in wild-type mesangial cells and stably transfected Smad4-DN cell lines in the absence and presence of TGF-β. Results As compared to wild-type MMC that had a 10.8-fold Stimulation of TGF-β–induced p3TP-Lux activity, MMC stably transfected with Smad4ΔM4 and Smad4N4 had only a 2.0-fold and 1.3-fold Stimulation, respectively, indicating that they had dominant-negative effects on TGF-β signaling. Basal and TGF-β–induced COL1A1 expression in Smad4 dominant-negative cells were dramatically reduced to very low levels. The early (2 hours) TGF-β–induced PAI-1 mRNA expression was inhibited; however, the sustained (24 to 48 hours) TGF-β–induced expression was not affected in Smad4 dominant-negative cells. For FN, TGF-β–induced expression was maintained in Smad4-dominant negative cells. Conclusion These results indicate that Smad4 is essential for basal and TGF-β–induced COL1A1 expression, and contributes to the early, but not sustained TGF-β–induced PAI-1 expression in mesangial cells. However, TGF-β–induced FN expression is independent of Smad4. In conclusion, Smad4 has a discriminate effect in mediating specific ECM molecules stimulated by TGF-β in mesangial cells.