The Experts below are selected from a list of 6129 Experts worldwide ranked by ideXlab platform

Bysani Chandrasekar - One of the best experts on this subject based on the ideXlab platform.

  • the nox1 4 dual inhibitor gkt137831 or nox4 knockdown inhibits angiotensin ii induced adult mouse Cardiac Fibroblast proliferation and migration at1 physically associates with nox4
    Journal of Cellular Physiology, 2016
    Co-Authors: Naveen K Somanna, Maike Krenz, Patrice Delafontaine, Anthony J Valente, Bysani Chandrasekar
    Abstract:

    Both oxidative stress and inflammation contribute to chronic hypertension-induced myocardial fibrosis and adverse Cardiac remodeling. Here we investigated whether angiotensin (Ang)-II-induced Fibroblast proliferation and migration are NADPH oxidase (Nox) 4/ROS and IL-18 dependent. Our results show that the potent induction of mouse Cardiac Fibroblast (CF) proliferation and migration by Ang-II is markedly attenuated by Nox4 knockdown and the Nox inhibitor DPI. Further, Nox4 knockdown and DPI pre-treatment attenuated Ang-II-induced IL-18, IL-18Rα and collagen expression, and MMP9 and LOX activation. While neutralization of IL-18 blunted Ang-II-induced CF proliferation and migration, knockdown of MMP9 attenuated CF migration. The antioxidant NAC and the cell-permeable SOD mimetics Tempol, MnTBAP, and MnTMPyP attenuated oxidative stress and inhibited CF proliferation and migration. The Nox1/Nox4 dual inhibitor GKT137831 also blunted Ang-II-induced H2O2 production and CF proliferation and migration. Further, AT1 bound Nox4, and Ang-II enhanced their physical association. Notably, GKT137831 attnuated the AT1/Nox4 interaction. These results indicate that Ang-II induces CF proliferation and migration in part via Nox4/ROS-dependent IL-18 induction and MMP9 activation, and may involve AT1/Nox4 physical association. Thus, either (i) neutralizing IL-18, (ii) blocking AT1/Nox4 interaction or (iii) use of the Nox1/Nox4 inhibitor GKT137831 may have therapeutic potential in chronic hypertension-induced adverse Cardiac remodeling. J. Cell. Physiol. 231: 1130–1141, 2016. © 2015 Wiley Periodicals, Inc.

  • the nox1 4 dual inhibitor gkt137831 or nox4 knockdown inhibits angiotensin ii induced adult mouse Cardiac Fibroblast proliferation and migration at1 physically associates with nox4
    Journal of Cellular Physiology, 2016
    Co-Authors: Naveen K Somanna, Maike Krenz, Patrice Delafontaine, Anthony J Valente, William P Fay, Bysani Chandrasekar
    Abstract:

    Both oxidative stress and inflammation contribute to chronic hypertension-induced myocardial fibrosis and adverse Cardiac remodeling. Here we investigated whether angiotensin (Ang)-II-induced Fibroblast proliferation and migration are NADPH oxidase (Nox) 4/ROS and IL-18 dependent. Our results show that the potent induction of mouse Cardiac Fibroblast (CF) proliferation and migration by Ang-II is markedly attenuated by Nox4 knockdown and the Nox inhibitor DPI. Further, Nox4 knockdown and DPI pre-treatment attenuated Ang-II-induced IL-18, IL-18Rα and collagen expression, and MMP9 and LOX activation. While neutralization of IL-18 blunted Ang-II-induced CF proliferation and migration, knockdown of MMP9 attenuated CF migration. The antioxidant NAC and the cell-permeable SOD mimetics Tempol, MnTBAP, and MnTMPyP attenuated oxidative stress and inhibited CF proliferation and migration. The Nox1/Nox4 dual inhibitor GKT137831 also blunted Ang-II-induced H2 O2 production and CF proliferation and migration. Further, AT1 bound Nox4, and Ang-II enhanced their physical association. Notably, GKT137831 attenuated the AT1/Nox4 interaction. These results indicate that Ang-II induces CF proliferation and migration in part via Nox4/ROS-dependent IL-18 induction and MMP9 activation, and may involve AT1/Nox4 physical association. Thus, either (i) neutralizing IL-18, (ii) blocking AT1/Nox4 interaction or (iii) use of the Nox1/Nox4 inhibitor GKT137831 may have therapeutic potential in chronic hypertension-induced adverse Cardiac remodeling.

  • docosahexaenoic acid reverses angiotensin ii induced reck suppression and Cardiac Fibroblast migration
    Cellular Signalling, 2014
    Co-Authors: Jalahalli M Siddesha, Bysani Chandrasekar, Patrice Delafontaine, Anthony J Valente, Tadashi Yoshida, Siva S V P Sakamuri, Hideo Iba, Makoto Noda
    Abstract:

    The omega-3 polyunsaturated fatty acids (ω-3 fatty acids) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been reported to inhibit or delay the progression of cardiovascular diseases, including myocardial fibrosis. Recently we reported that angiotensin II (Ang II) promotes Cardiac Fibroblast (CF) migration by suppressing the MMP regulator reversion-inducing-cysteine-rich protein with Kazal motifs (RECK), through a mechanism dependent on AT1, ERK, and Sp1. Here we investigated the role of miR-21 in Ang II-mediated RECK suppression, and determined whether the ω-3 fatty acids reverse these effects. Ang II induced miR-21 expression in primary mouse Cardiac Fibroblasts (CFs) via ERK-dependent AP-1 and STAT3 activation, and while a miR-21 inhibitor reversed Ang II-induced RECK suppression, a miR-21 mimic inhibited both RECK expression and Ang II-induced CF migration. Moreover, Ang II suppressed the pro-apoptotic PTEN, and the ERK negative regulator Sprouty homologue 1 (SPRY1), but induced the metalloendopeptidase MMP2, all in a manner that was miR-21-dependent. Further, forced expression of PTEN inhibited Akt phosphorylation, Sp1 activation, and MMP2 induction. Notably, while both EPA and DHA reversed Ang II-mediated RECK suppression, DHA appeared to be more effective, and reversed Ang II-induced miR-21 expression, RECK suppression, MMP2 induction, and CF migration. These results indicate that Ang II-induced CF migration is differentially regulated by miR-21-mediated MMP induction and RECK suppression, and that DHA has the potential to upregulate RECK, and therefore may exert potential beneficial effects in Cardiac fibrosis.

  • interleukin 17a stimulates Cardiac Fibroblast proliferation and migration via negative regulation of the dual specificity phosphatase mkp 1 dusp 1
    Cellular Signalling, 2012
    Co-Authors: Anthony J Valente, Naveen K Somanna, Patrice Delafontaine, Tadashi Yoshida, Jason D Gardner, Bysani Chandrasekar
    Abstract:

    The dual-specificity mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) inactivates MAP kinases by dephosphorylation. Here we show that the proinflammatory cytokine interleukin (IL)-17A induces adult mouse primary Cardiac Fibroblast (CF) proliferation and migration via IL-17 receptor A//IL-17 receptor C-dependent MKP-1 suppression, and activation of p38 MAPK and ERK1/2. IL-17A mediated p38 MAPK and ERK1/2 activation is inhibited by MKP-1 overexpression, but prolonged by MKP-1 knockdown. IL-17A induced miR-101 expression via PI3K/Akt, and miR-101 inhibitor reversed MKP-1 down regulation. Importantly, MKP-1 knockdown, inhibition of p38 MAPK by SB 203580, inhibition of ERK1/2 by U0126 and PD 98059, or overexpression of dominant negative MEK1, each markedly attenuated IL-17A-mediated CF proliferation and migration. Similarly, IL-17F and IL-17A/F heterodimer that also signal via IL-17RA/IL-17RC, stimulated CF proliferation and migration. These results indicate that IL-17A stimulates CF proliferation and migration via Akt/miR-101/MKP-1-dependent p38 MAPK and ERK1/2 activation. These studies support a potential role for IL-17 in Cardiac fibrosis and adverse myocardial remodeling.

Anthony J Valente - One of the best experts on this subject based on the ideXlab platform.

  • the nox1 4 dual inhibitor gkt137831 or nox4 knockdown inhibits angiotensin ii induced adult mouse Cardiac Fibroblast proliferation and migration at1 physically associates with nox4
    Journal of Cellular Physiology, 2016
    Co-Authors: Naveen K Somanna, Maike Krenz, Patrice Delafontaine, Anthony J Valente, Bysani Chandrasekar
    Abstract:

    Both oxidative stress and inflammation contribute to chronic hypertension-induced myocardial fibrosis and adverse Cardiac remodeling. Here we investigated whether angiotensin (Ang)-II-induced Fibroblast proliferation and migration are NADPH oxidase (Nox) 4/ROS and IL-18 dependent. Our results show that the potent induction of mouse Cardiac Fibroblast (CF) proliferation and migration by Ang-II is markedly attenuated by Nox4 knockdown and the Nox inhibitor DPI. Further, Nox4 knockdown and DPI pre-treatment attenuated Ang-II-induced IL-18, IL-18Rα and collagen expression, and MMP9 and LOX activation. While neutralization of IL-18 blunted Ang-II-induced CF proliferation and migration, knockdown of MMP9 attenuated CF migration. The antioxidant NAC and the cell-permeable SOD mimetics Tempol, MnTBAP, and MnTMPyP attenuated oxidative stress and inhibited CF proliferation and migration. The Nox1/Nox4 dual inhibitor GKT137831 also blunted Ang-II-induced H2O2 production and CF proliferation and migration. Further, AT1 bound Nox4, and Ang-II enhanced their physical association. Notably, GKT137831 attnuated the AT1/Nox4 interaction. These results indicate that Ang-II induces CF proliferation and migration in part via Nox4/ROS-dependent IL-18 induction and MMP9 activation, and may involve AT1/Nox4 physical association. Thus, either (i) neutralizing IL-18, (ii) blocking AT1/Nox4 interaction or (iii) use of the Nox1/Nox4 inhibitor GKT137831 may have therapeutic potential in chronic hypertension-induced adverse Cardiac remodeling. J. Cell. Physiol. 231: 1130–1141, 2016. © 2015 Wiley Periodicals, Inc.

  • the nox1 4 dual inhibitor gkt137831 or nox4 knockdown inhibits angiotensin ii induced adult mouse Cardiac Fibroblast proliferation and migration at1 physically associates with nox4
    Journal of Cellular Physiology, 2016
    Co-Authors: Naveen K Somanna, Maike Krenz, Patrice Delafontaine, Anthony J Valente, William P Fay, Bysani Chandrasekar
    Abstract:

    Both oxidative stress and inflammation contribute to chronic hypertension-induced myocardial fibrosis and adverse Cardiac remodeling. Here we investigated whether angiotensin (Ang)-II-induced Fibroblast proliferation and migration are NADPH oxidase (Nox) 4/ROS and IL-18 dependent. Our results show that the potent induction of mouse Cardiac Fibroblast (CF) proliferation and migration by Ang-II is markedly attenuated by Nox4 knockdown and the Nox inhibitor DPI. Further, Nox4 knockdown and DPI pre-treatment attenuated Ang-II-induced IL-18, IL-18Rα and collagen expression, and MMP9 and LOX activation. While neutralization of IL-18 blunted Ang-II-induced CF proliferation and migration, knockdown of MMP9 attenuated CF migration. The antioxidant NAC and the cell-permeable SOD mimetics Tempol, MnTBAP, and MnTMPyP attenuated oxidative stress and inhibited CF proliferation and migration. The Nox1/Nox4 dual inhibitor GKT137831 also blunted Ang-II-induced H2 O2 production and CF proliferation and migration. Further, AT1 bound Nox4, and Ang-II enhanced their physical association. Notably, GKT137831 attenuated the AT1/Nox4 interaction. These results indicate that Ang-II induces CF proliferation and migration in part via Nox4/ROS-dependent IL-18 induction and MMP9 activation, and may involve AT1/Nox4 physical association. Thus, either (i) neutralizing IL-18, (ii) blocking AT1/Nox4 interaction or (iii) use of the Nox1/Nox4 inhibitor GKT137831 may have therapeutic potential in chronic hypertension-induced adverse Cardiac remodeling.

  • docosahexaenoic acid reverses angiotensin ii induced reck suppression and Cardiac Fibroblast migration
    Cellular Signalling, 2014
    Co-Authors: Jalahalli M Siddesha, Bysani Chandrasekar, Patrice Delafontaine, Anthony J Valente, Tadashi Yoshida, Siva S V P Sakamuri, Hideo Iba, Makoto Noda
    Abstract:

    The omega-3 polyunsaturated fatty acids (ω-3 fatty acids) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been reported to inhibit or delay the progression of cardiovascular diseases, including myocardial fibrosis. Recently we reported that angiotensin II (Ang II) promotes Cardiac Fibroblast (CF) migration by suppressing the MMP regulator reversion-inducing-cysteine-rich protein with Kazal motifs (RECK), through a mechanism dependent on AT1, ERK, and Sp1. Here we investigated the role of miR-21 in Ang II-mediated RECK suppression, and determined whether the ω-3 fatty acids reverse these effects. Ang II induced miR-21 expression in primary mouse Cardiac Fibroblasts (CFs) via ERK-dependent AP-1 and STAT3 activation, and while a miR-21 inhibitor reversed Ang II-induced RECK suppression, a miR-21 mimic inhibited both RECK expression and Ang II-induced CF migration. Moreover, Ang II suppressed the pro-apoptotic PTEN, and the ERK negative regulator Sprouty homologue 1 (SPRY1), but induced the metalloendopeptidase MMP2, all in a manner that was miR-21-dependent. Further, forced expression of PTEN inhibited Akt phosphorylation, Sp1 activation, and MMP2 induction. Notably, while both EPA and DHA reversed Ang II-mediated RECK suppression, DHA appeared to be more effective, and reversed Ang II-induced miR-21 expression, RECK suppression, MMP2 induction, and CF migration. These results indicate that Ang II-induced CF migration is differentially regulated by miR-21-mediated MMP induction and RECK suppression, and that DHA has the potential to upregulate RECK, and therefore may exert potential beneficial effects in Cardiac fibrosis.

  • interleukin 17a stimulates Cardiac Fibroblast proliferation and migration via negative regulation of the dual specificity phosphatase mkp 1 dusp 1
    Cellular Signalling, 2012
    Co-Authors: Anthony J Valente, Naveen K Somanna, Patrice Delafontaine, Tadashi Yoshida, Jason D Gardner, Bysani Chandrasekar
    Abstract:

    The dual-specificity mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) inactivates MAP kinases by dephosphorylation. Here we show that the proinflammatory cytokine interleukin (IL)-17A induces adult mouse primary Cardiac Fibroblast (CF) proliferation and migration via IL-17 receptor A//IL-17 receptor C-dependent MKP-1 suppression, and activation of p38 MAPK and ERK1/2. IL-17A mediated p38 MAPK and ERK1/2 activation is inhibited by MKP-1 overexpression, but prolonged by MKP-1 knockdown. IL-17A induced miR-101 expression via PI3K/Akt, and miR-101 inhibitor reversed MKP-1 down regulation. Importantly, MKP-1 knockdown, inhibition of p38 MAPK by SB 203580, inhibition of ERK1/2 by U0126 and PD 98059, or overexpression of dominant negative MEK1, each markedly attenuated IL-17A-mediated CF proliferation and migration. Similarly, IL-17F and IL-17A/F heterodimer that also signal via IL-17RA/IL-17RC, stimulated CF proliferation and migration. These results indicate that IL-17A stimulates CF proliferation and migration via Akt/miR-101/MKP-1-dependent p38 MAPK and ERK1/2 activation. These studies support a potential role for IL-17 in Cardiac fibrosis and adverse myocardial remodeling.

Naveen K Somanna - One of the best experts on this subject based on the ideXlab platform.

  • the nox1 4 dual inhibitor gkt137831 or nox4 knockdown inhibits angiotensin ii induced adult mouse Cardiac Fibroblast proliferation and migration at1 physically associates with nox4
    Journal of Cellular Physiology, 2016
    Co-Authors: Naveen K Somanna, Maike Krenz, Patrice Delafontaine, Anthony J Valente, Bysani Chandrasekar
    Abstract:

    Both oxidative stress and inflammation contribute to chronic hypertension-induced myocardial fibrosis and adverse Cardiac remodeling. Here we investigated whether angiotensin (Ang)-II-induced Fibroblast proliferation and migration are NADPH oxidase (Nox) 4/ROS and IL-18 dependent. Our results show that the potent induction of mouse Cardiac Fibroblast (CF) proliferation and migration by Ang-II is markedly attenuated by Nox4 knockdown and the Nox inhibitor DPI. Further, Nox4 knockdown and DPI pre-treatment attenuated Ang-II-induced IL-18, IL-18Rα and collagen expression, and MMP9 and LOX activation. While neutralization of IL-18 blunted Ang-II-induced CF proliferation and migration, knockdown of MMP9 attenuated CF migration. The antioxidant NAC and the cell-permeable SOD mimetics Tempol, MnTBAP, and MnTMPyP attenuated oxidative stress and inhibited CF proliferation and migration. The Nox1/Nox4 dual inhibitor GKT137831 also blunted Ang-II-induced H2O2 production and CF proliferation and migration. Further, AT1 bound Nox4, and Ang-II enhanced their physical association. Notably, GKT137831 attnuated the AT1/Nox4 interaction. These results indicate that Ang-II induces CF proliferation and migration in part via Nox4/ROS-dependent IL-18 induction and MMP9 activation, and may involve AT1/Nox4 physical association. Thus, either (i) neutralizing IL-18, (ii) blocking AT1/Nox4 interaction or (iii) use of the Nox1/Nox4 inhibitor GKT137831 may have therapeutic potential in chronic hypertension-induced adverse Cardiac remodeling. J. Cell. Physiol. 231: 1130–1141, 2016. © 2015 Wiley Periodicals, Inc.

  • the nox1 4 dual inhibitor gkt137831 or nox4 knockdown inhibits angiotensin ii induced adult mouse Cardiac Fibroblast proliferation and migration at1 physically associates with nox4
    Journal of Cellular Physiology, 2016
    Co-Authors: Naveen K Somanna, Maike Krenz, Patrice Delafontaine, Anthony J Valente, William P Fay, Bysani Chandrasekar
    Abstract:

    Both oxidative stress and inflammation contribute to chronic hypertension-induced myocardial fibrosis and adverse Cardiac remodeling. Here we investigated whether angiotensin (Ang)-II-induced Fibroblast proliferation and migration are NADPH oxidase (Nox) 4/ROS and IL-18 dependent. Our results show that the potent induction of mouse Cardiac Fibroblast (CF) proliferation and migration by Ang-II is markedly attenuated by Nox4 knockdown and the Nox inhibitor DPI. Further, Nox4 knockdown and DPI pre-treatment attenuated Ang-II-induced IL-18, IL-18Rα and collagen expression, and MMP9 and LOX activation. While neutralization of IL-18 blunted Ang-II-induced CF proliferation and migration, knockdown of MMP9 attenuated CF migration. The antioxidant NAC and the cell-permeable SOD mimetics Tempol, MnTBAP, and MnTMPyP attenuated oxidative stress and inhibited CF proliferation and migration. The Nox1/Nox4 dual inhibitor GKT137831 also blunted Ang-II-induced H2 O2 production and CF proliferation and migration. Further, AT1 bound Nox4, and Ang-II enhanced their physical association. Notably, GKT137831 attenuated the AT1/Nox4 interaction. These results indicate that Ang-II induces CF proliferation and migration in part via Nox4/ROS-dependent IL-18 induction and MMP9 activation, and may involve AT1/Nox4 physical association. Thus, either (i) neutralizing IL-18, (ii) blocking AT1/Nox4 interaction or (iii) use of the Nox1/Nox4 inhibitor GKT137831 may have therapeutic potential in chronic hypertension-induced adverse Cardiac remodeling.

  • interleukin 17a stimulates Cardiac Fibroblast proliferation and migration via negative regulation of the dual specificity phosphatase mkp 1 dusp 1
    Cellular Signalling, 2012
    Co-Authors: Anthony J Valente, Naveen K Somanna, Patrice Delafontaine, Tadashi Yoshida, Jason D Gardner, Bysani Chandrasekar
    Abstract:

    The dual-specificity mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) inactivates MAP kinases by dephosphorylation. Here we show that the proinflammatory cytokine interleukin (IL)-17A induces adult mouse primary Cardiac Fibroblast (CF) proliferation and migration via IL-17 receptor A//IL-17 receptor C-dependent MKP-1 suppression, and activation of p38 MAPK and ERK1/2. IL-17A mediated p38 MAPK and ERK1/2 activation is inhibited by MKP-1 overexpression, but prolonged by MKP-1 knockdown. IL-17A induced miR-101 expression via PI3K/Akt, and miR-101 inhibitor reversed MKP-1 down regulation. Importantly, MKP-1 knockdown, inhibition of p38 MAPK by SB 203580, inhibition of ERK1/2 by U0126 and PD 98059, or overexpression of dominant negative MEK1, each markedly attenuated IL-17A-mediated CF proliferation and migration. Similarly, IL-17F and IL-17A/F heterodimer that also signal via IL-17RA/IL-17RC, stimulated CF proliferation and migration. These results indicate that IL-17A stimulates CF proliferation and migration via Akt/miR-101/MKP-1-dependent p38 MAPK and ERK1/2 activation. These studies support a potential role for IL-17 in Cardiac fibrosis and adverse myocardial remodeling.

Patrice Delafontaine - One of the best experts on this subject based on the ideXlab platform.

  • the nox1 4 dual inhibitor gkt137831 or nox4 knockdown inhibits angiotensin ii induced adult mouse Cardiac Fibroblast proliferation and migration at1 physically associates with nox4
    Journal of Cellular Physiology, 2016
    Co-Authors: Naveen K Somanna, Maike Krenz, Patrice Delafontaine, Anthony J Valente, Bysani Chandrasekar
    Abstract:

    Both oxidative stress and inflammation contribute to chronic hypertension-induced myocardial fibrosis and adverse Cardiac remodeling. Here we investigated whether angiotensin (Ang)-II-induced Fibroblast proliferation and migration are NADPH oxidase (Nox) 4/ROS and IL-18 dependent. Our results show that the potent induction of mouse Cardiac Fibroblast (CF) proliferation and migration by Ang-II is markedly attenuated by Nox4 knockdown and the Nox inhibitor DPI. Further, Nox4 knockdown and DPI pre-treatment attenuated Ang-II-induced IL-18, IL-18Rα and collagen expression, and MMP9 and LOX activation. While neutralization of IL-18 blunted Ang-II-induced CF proliferation and migration, knockdown of MMP9 attenuated CF migration. The antioxidant NAC and the cell-permeable SOD mimetics Tempol, MnTBAP, and MnTMPyP attenuated oxidative stress and inhibited CF proliferation and migration. The Nox1/Nox4 dual inhibitor GKT137831 also blunted Ang-II-induced H2O2 production and CF proliferation and migration. Further, AT1 bound Nox4, and Ang-II enhanced their physical association. Notably, GKT137831 attnuated the AT1/Nox4 interaction. These results indicate that Ang-II induces CF proliferation and migration in part via Nox4/ROS-dependent IL-18 induction and MMP9 activation, and may involve AT1/Nox4 physical association. Thus, either (i) neutralizing IL-18, (ii) blocking AT1/Nox4 interaction or (iii) use of the Nox1/Nox4 inhibitor GKT137831 may have therapeutic potential in chronic hypertension-induced adverse Cardiac remodeling. J. Cell. Physiol. 231: 1130–1141, 2016. © 2015 Wiley Periodicals, Inc.

  • the nox1 4 dual inhibitor gkt137831 or nox4 knockdown inhibits angiotensin ii induced adult mouse Cardiac Fibroblast proliferation and migration at1 physically associates with nox4
    Journal of Cellular Physiology, 2016
    Co-Authors: Naveen K Somanna, Maike Krenz, Patrice Delafontaine, Anthony J Valente, William P Fay, Bysani Chandrasekar
    Abstract:

    Both oxidative stress and inflammation contribute to chronic hypertension-induced myocardial fibrosis and adverse Cardiac remodeling. Here we investigated whether angiotensin (Ang)-II-induced Fibroblast proliferation and migration are NADPH oxidase (Nox) 4/ROS and IL-18 dependent. Our results show that the potent induction of mouse Cardiac Fibroblast (CF) proliferation and migration by Ang-II is markedly attenuated by Nox4 knockdown and the Nox inhibitor DPI. Further, Nox4 knockdown and DPI pre-treatment attenuated Ang-II-induced IL-18, IL-18Rα and collagen expression, and MMP9 and LOX activation. While neutralization of IL-18 blunted Ang-II-induced CF proliferation and migration, knockdown of MMP9 attenuated CF migration. The antioxidant NAC and the cell-permeable SOD mimetics Tempol, MnTBAP, and MnTMPyP attenuated oxidative stress and inhibited CF proliferation and migration. The Nox1/Nox4 dual inhibitor GKT137831 also blunted Ang-II-induced H2 O2 production and CF proliferation and migration. Further, AT1 bound Nox4, and Ang-II enhanced their physical association. Notably, GKT137831 attenuated the AT1/Nox4 interaction. These results indicate that Ang-II induces CF proliferation and migration in part via Nox4/ROS-dependent IL-18 induction and MMP9 activation, and may involve AT1/Nox4 physical association. Thus, either (i) neutralizing IL-18, (ii) blocking AT1/Nox4 interaction or (iii) use of the Nox1/Nox4 inhibitor GKT137831 may have therapeutic potential in chronic hypertension-induced adverse Cardiac remodeling.

  • docosahexaenoic acid reverses angiotensin ii induced reck suppression and Cardiac Fibroblast migration
    Cellular Signalling, 2014
    Co-Authors: Jalahalli M Siddesha, Bysani Chandrasekar, Patrice Delafontaine, Anthony J Valente, Tadashi Yoshida, Siva S V P Sakamuri, Hideo Iba, Makoto Noda
    Abstract:

    The omega-3 polyunsaturated fatty acids (ω-3 fatty acids) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been reported to inhibit or delay the progression of cardiovascular diseases, including myocardial fibrosis. Recently we reported that angiotensin II (Ang II) promotes Cardiac Fibroblast (CF) migration by suppressing the MMP regulator reversion-inducing-cysteine-rich protein with Kazal motifs (RECK), through a mechanism dependent on AT1, ERK, and Sp1. Here we investigated the role of miR-21 in Ang II-mediated RECK suppression, and determined whether the ω-3 fatty acids reverse these effects. Ang II induced miR-21 expression in primary mouse Cardiac Fibroblasts (CFs) via ERK-dependent AP-1 and STAT3 activation, and while a miR-21 inhibitor reversed Ang II-induced RECK suppression, a miR-21 mimic inhibited both RECK expression and Ang II-induced CF migration. Moreover, Ang II suppressed the pro-apoptotic PTEN, and the ERK negative regulator Sprouty homologue 1 (SPRY1), but induced the metalloendopeptidase MMP2, all in a manner that was miR-21-dependent. Further, forced expression of PTEN inhibited Akt phosphorylation, Sp1 activation, and MMP2 induction. Notably, while both EPA and DHA reversed Ang II-mediated RECK suppression, DHA appeared to be more effective, and reversed Ang II-induced miR-21 expression, RECK suppression, MMP2 induction, and CF migration. These results indicate that Ang II-induced CF migration is differentially regulated by miR-21-mediated MMP induction and RECK suppression, and that DHA has the potential to upregulate RECK, and therefore may exert potential beneficial effects in Cardiac fibrosis.

  • interleukin 17a stimulates Cardiac Fibroblast proliferation and migration via negative regulation of the dual specificity phosphatase mkp 1 dusp 1
    Cellular Signalling, 2012
    Co-Authors: Anthony J Valente, Naveen K Somanna, Patrice Delafontaine, Tadashi Yoshida, Jason D Gardner, Bysani Chandrasekar
    Abstract:

    The dual-specificity mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) inactivates MAP kinases by dephosphorylation. Here we show that the proinflammatory cytokine interleukin (IL)-17A induces adult mouse primary Cardiac Fibroblast (CF) proliferation and migration via IL-17 receptor A//IL-17 receptor C-dependent MKP-1 suppression, and activation of p38 MAPK and ERK1/2. IL-17A mediated p38 MAPK and ERK1/2 activation is inhibited by MKP-1 overexpression, but prolonged by MKP-1 knockdown. IL-17A induced miR-101 expression via PI3K/Akt, and miR-101 inhibitor reversed MKP-1 down regulation. Importantly, MKP-1 knockdown, inhibition of p38 MAPK by SB 203580, inhibition of ERK1/2 by U0126 and PD 98059, or overexpression of dominant negative MEK1, each markedly attenuated IL-17A-mediated CF proliferation and migration. Similarly, IL-17F and IL-17A/F heterodimer that also signal via IL-17RA/IL-17RC, stimulated CF proliferation and migration. These results indicate that IL-17A stimulates CF proliferation and migration via Akt/miR-101/MKP-1-dependent p38 MAPK and ERK1/2 activation. These studies support a potential role for IL-17 in Cardiac fibrosis and adverse myocardial remodeling.

Maike Krenz - One of the best experts on this subject based on the ideXlab platform.

  • the nox1 4 dual inhibitor gkt137831 or nox4 knockdown inhibits angiotensin ii induced adult mouse Cardiac Fibroblast proliferation and migration at1 physically associates with nox4
    Journal of Cellular Physiology, 2016
    Co-Authors: Naveen K Somanna, Maike Krenz, Patrice Delafontaine, Anthony J Valente, Bysani Chandrasekar
    Abstract:

    Both oxidative stress and inflammation contribute to chronic hypertension-induced myocardial fibrosis and adverse Cardiac remodeling. Here we investigated whether angiotensin (Ang)-II-induced Fibroblast proliferation and migration are NADPH oxidase (Nox) 4/ROS and IL-18 dependent. Our results show that the potent induction of mouse Cardiac Fibroblast (CF) proliferation and migration by Ang-II is markedly attenuated by Nox4 knockdown and the Nox inhibitor DPI. Further, Nox4 knockdown and DPI pre-treatment attenuated Ang-II-induced IL-18, IL-18Rα and collagen expression, and MMP9 and LOX activation. While neutralization of IL-18 blunted Ang-II-induced CF proliferation and migration, knockdown of MMP9 attenuated CF migration. The antioxidant NAC and the cell-permeable SOD mimetics Tempol, MnTBAP, and MnTMPyP attenuated oxidative stress and inhibited CF proliferation and migration. The Nox1/Nox4 dual inhibitor GKT137831 also blunted Ang-II-induced H2O2 production and CF proliferation and migration. Further, AT1 bound Nox4, and Ang-II enhanced their physical association. Notably, GKT137831 attnuated the AT1/Nox4 interaction. These results indicate that Ang-II induces CF proliferation and migration in part via Nox4/ROS-dependent IL-18 induction and MMP9 activation, and may involve AT1/Nox4 physical association. Thus, either (i) neutralizing IL-18, (ii) blocking AT1/Nox4 interaction or (iii) use of the Nox1/Nox4 inhibitor GKT137831 may have therapeutic potential in chronic hypertension-induced adverse Cardiac remodeling. J. Cell. Physiol. 231: 1130–1141, 2016. © 2015 Wiley Periodicals, Inc.

  • the nox1 4 dual inhibitor gkt137831 or nox4 knockdown inhibits angiotensin ii induced adult mouse Cardiac Fibroblast proliferation and migration at1 physically associates with nox4
    Journal of Cellular Physiology, 2016
    Co-Authors: Naveen K Somanna, Maike Krenz, Patrice Delafontaine, Anthony J Valente, William P Fay, Bysani Chandrasekar
    Abstract:

    Both oxidative stress and inflammation contribute to chronic hypertension-induced myocardial fibrosis and adverse Cardiac remodeling. Here we investigated whether angiotensin (Ang)-II-induced Fibroblast proliferation and migration are NADPH oxidase (Nox) 4/ROS and IL-18 dependent. Our results show that the potent induction of mouse Cardiac Fibroblast (CF) proliferation and migration by Ang-II is markedly attenuated by Nox4 knockdown and the Nox inhibitor DPI. Further, Nox4 knockdown and DPI pre-treatment attenuated Ang-II-induced IL-18, IL-18Rα and collagen expression, and MMP9 and LOX activation. While neutralization of IL-18 blunted Ang-II-induced CF proliferation and migration, knockdown of MMP9 attenuated CF migration. The antioxidant NAC and the cell-permeable SOD mimetics Tempol, MnTBAP, and MnTMPyP attenuated oxidative stress and inhibited CF proliferation and migration. The Nox1/Nox4 dual inhibitor GKT137831 also blunted Ang-II-induced H2 O2 production and CF proliferation and migration. Further, AT1 bound Nox4, and Ang-II enhanced their physical association. Notably, GKT137831 attenuated the AT1/Nox4 interaction. These results indicate that Ang-II induces CF proliferation and migration in part via Nox4/ROS-dependent IL-18 induction and MMP9 activation, and may involve AT1/Nox4 physical association. Thus, either (i) neutralizing IL-18, (ii) blocking AT1/Nox4 interaction or (iii) use of the Nox1/Nox4 inhibitor GKT137831 may have therapeutic potential in chronic hypertension-induced adverse Cardiac remodeling.