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10.18632/oncotarget.15825 http://scihub22266oqcxt.onion/10.18632/oncotarget.15825 C5464828!5464828!28427181     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Oncotarget 2017 ; 8 (20): 32794-806 Nephropedia Template TP {{tp|p=28427181|t=2017. Metformin inhibits ALK1-mediated angiogenesis via activation of AMPK |pdf=|usr=}}{{28427181}} gab.com Text Metformin inhibits ALK1-mediated angiogenesis via activation of AMPK JO: Oncotarget http://www.kidney.de/pget.php?&tw=1&pmid=28427181 #FOAvip Anti-VEGF therapy has been proven to be effective in the treatment of pathological angiogenesis. However, therapy resistance often occurs, leading to development of alternative approaches. The present study examines if AMPK negatively regulates ALK1-mediated signaling events and associated angiogenesis. Thus, we treated human umbilical vein endothelial cells with metformin as well as other pharmacological AMPK activators and showed that activation of AMPK inhibited Smad1/5 phosphorylation and tube formation induced by BMP9. This event was mimicked by expression of the active mutant of AMPK?1 and prevented by the dominant negative AMPK?1. Metformin inhibition of BMP9 signaling is possibly mediated by upregulation of Smurf1, leading to degradation of ALK1. Furthermore, metformin suppressed BMP9-induced angiogenesis in mouse matrigel plug. In addition, laser photocoagulation was employed to evaluate the effect of metformin. The data revealed that metformin significantly reduced choroidal neovascularization to a level comparable to LDN212854, an ALK1 specific inhibitor. In conjunction, metformin diminished expression of ALK1 in endothelium of the lesion area. Collectively, our study for the first time demonstrates that AMPK inhibits ALK1 and associated angiogenesis/neovascularization. This may offer us a new avenue for the treatment of related diseases using clinically used pharmacological AMPK activators like metformin in combination with other strategies to enhance the treatment efficacy or in the case of anti-VEGF resistance. Twit Text FOAVip Metformin inhibits ALK1-mediated angiogenesis via activation of AMPK ????Oncotarget http://www.kidney.de/pget.php?&tw=1&pmid=28427181 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28427181 #FOAvip English Wikipedia <ref>{{Cite pmid|28427181}}</ref> Metformin inhibits ALK1-mediated angiogenesis via activation of AMPK #MMPMID28427181 Ying Y; Ueta T; Jiang S; Lin H; Wang Y; Vavvas D; Wen R; Chen YG; Luo Z Oncotarget 2017[May]; 8 (20): 32794-806 PMID28427181show ga Anti-VEGF therapy has been proven to be effective in the treatment of pathological angiogenesis. However, therapy resistance often occurs, leading to development of alternative approaches. The present study examines if AMPK negatively regulates ALK1-mediated signaling events and associated angiogenesis. Thus, we treated human umbilical vein endothelial cells with metformin as well as other pharmacological AMPK activators and showed that activation of AMPK inhibited Smad1/5 phosphorylation and tube formation induced by BMP9. This event was mimicked by expression of the active mutant of AMPK?1 and prevented by the dominant negative AMPK?1. Metformin inhibition of BMP9 signaling is possibly mediated by upregulation of Smurf1, leading to degradation of ALK1. Furthermore, metformin suppressed BMP9-induced angiogenesis in mouse matrigel plug. In addition, laser photocoagulation was employed to evaluate the effect of metformin. The data revealed that metformin significantly reduced choroidal neovascularization to a level comparable to LDN212854, an ALK1 specific inhibitor. In conjunction, metformin diminished expression of ALK1 in endothelium of the lesion area. Collectively, our study for the first time demonstrates that AMPK inhibits ALK1 and associated angiogenesis/neovascularization. This may offer us a new avenue for the treatment of related diseases using clinically used pharmacological AMPK activators like metformin in combination with other strategies to enhance the treatment efficacy or in the case of anti-VEGF resistance. äMetformin inhibits ALK1-mediated angiogenesis via activation of AMPK (epmc).pdf DeepDyve Pubget Overpricing