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10.1007/s00125-017-4214-6 http://scihub22266oqcxt.onion/10.1007/s00125-017-4214-6 C5342922!5342922!28116460     free     free     free Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Diabetologia 2017 ; 60 (4): 740-50 Nephropedia Template TP {{tp|p=28116460|t=2017. Enhanced VEGF signalling mediates cerebral neovascularisation via downregulation of guidance protein ROBO4 in a rat model of diabetes |pdf=|usr=}}{{28116460}} gab.com Text Enhanced VEGF signalling mediates cerebral neovascularisation via downregulation of guidance protein ROBO4 in a rat model of diabetes JO: Diabetologia http://www.kidney.de/pget.php?&tw=1&pmid=28116460 #FOAvip Aims/hypothesis: Diabetes promotes cerebral neovascularisation via increased vascular endothelial growth factor (VEGF) angiogenic signalling. Roundabout-4 (ROBO4) protein is an endogenous inhibitor of VEGF signalling that stabilises the vasculature. Yet, how diabetes affects ROBO4 function remains unknown. We hypothesised that increased VEGF signalling in diabetes decreases ROBO4 expression and function via binding of ROBO4 with VEGF-activated ?3 integrin and that restoration of ROBO4 expression prevents/repairs cerebral neovascularisation in diabetes. Methods: ROBO4 protein expression in a rat model of type 2 diabetes (Goto?Kakizaki [GK] rats) was examined by western blotting and immunohistochemistry. ROBO4 was locally overexpressed in the brain and in primary brain microvascular endothelial cells (BMVECs). GK rats were treated with SKLB1002, a selective VEGF receptor-2 (VEGFR-2) antagonist. Cerebrovascular neovascularisation indices were determined using an FITC vascular space-filling model. Immunoprecipitation was used to determine ROBO4??3 integrin interaction. Results: ROBO4 expression was significantly decreased in the cerebral vasculature as well as in BMVECs in diabetes (p<0.05). Silencing Robo4 increased the angiogenic properties of control BMVECs (p<0.05). In vivo and in vitro overexpression of ROBO4 inhibited VEGF-induced angiogenic signalling and increased vessel maturation. Inhibition of VEGF signalling using SKLB1002 increased ROBO4 expression (p<0.05) and reduced neovascularisation indices (p<0.05). Furthermore, SLKB1002 significantly decreased ROBO4??3 integrin interaction in diabetes (p<0.05). Conclusions/interpretation: Our study identifies the restoration of ROBO4 and inhibition of VEGF signalling as treatment strategies for diabetes-induced cerebral neovascularisation. Twit Text FOAVip Enhanced VEGF signalling mediates cerebral neovascularisation via downregulation of guidance protein ROBO4 in a rat model of diabetes ????Diabetologia http://www.kidney.de/pget.php?&tw=1&pmid=28116460 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28116460 #FOAvip English Wikipedia <ref>{{Cite pmid|28116460}}</ref> Enhanced VEGF signalling mediates cerebral neovascularisation via downregulation of guidance protein ROBO4 in a rat model of diabetes #MMPMID28116460 Abdelsaid M; Coucha M; Hafez S; Yasir A; Johnson MH; Ergul A Diabetologia 2017[Apr]; 60 (4): 740-50 PMID28116460show ga Aims/hypothesis: Diabetes promotes cerebral neovascularisation via increased vascular endothelial growth factor (VEGF) angiogenic signalling. Roundabout-4 (ROBO4) protein is an endogenous inhibitor of VEGF signalling that stabilises the vasculature. Yet, how diabetes affects ROBO4 function remains unknown. We hypothesised that increased VEGF signalling in diabetes decreases ROBO4 expression and function via binding of ROBO4 with VEGF-activated ?3 integrin and that restoration of ROBO4 expression prevents/repairs cerebral neovascularisation in diabetes. Methods: ROBO4 protein expression in a rat model of type 2 diabetes (Goto?Kakizaki [GK] rats) was examined by western blotting and immunohistochemistry. ROBO4 was locally overexpressed in the brain and in primary brain microvascular endothelial cells (BMVECs). GK rats were treated with SKLB1002, a selective VEGF receptor-2 (VEGFR-2) antagonist. Cerebrovascular neovascularisation indices were determined using an FITC vascular space-filling model. Immunoprecipitation was used to determine ROBO4??3 integrin interaction. Results: ROBO4 expression was significantly decreased in the cerebral vasculature as well as in BMVECs in diabetes (p<0.05). Silencing Robo4 increased the angiogenic properties of control BMVECs (p<0.05). In vivo and in vitro overexpression of ROBO4 inhibited VEGF-induced angiogenic signalling and increased vessel maturation. Inhibition of VEGF signalling using SKLB1002 increased ROBO4 expression (p<0.05) and reduced neovascularisation indices (p<0.05). Furthermore, SLKB1002 significantly decreased ROBO4??3 integrin interaction in diabetes (p<0.05). Conclusions/interpretation: Our study identifies the restoration of ROBO4 and inhibition of VEGF signalling as treatment strategies for diabetes-induced cerebral neovascularisation. äEnhanced VEGF signalling mediates cerebral neovascularisation via down(epmc).pdf DeepDyve Pubget Overpricing