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10.18632/oncotarget.15472 http://scihub22266oqcxt.onion/10.18632/oncotarget.15472 C5400562!5400562 !28423499     free     free     free Deprecated: Implicit conversion from float 215.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 215.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 215.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 215.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 215.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 215.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 215.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 249.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 249.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 249.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\28423499 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Oncotarget 2017 ; 8 (13 ): 21015-21030 Nephropedia Template TP {{tp|p=28423499 |t=2017. Imidazoline I2 receptor inhibitor idazoxan regulates the progression of hepatic fibrosis via Akt-Nrf2-Smad2/3 signaling pathway |pdf=|usr=}}{{28423499 }} gab.com Text Imidazoline I2 receptor inhibitor idazoxan regulates the progression of hepatic fibrosis via Akt-Nrf2-Smad2/3 signaling pathway JO: Oncotarget http://www.kidney.de/pget.php?&tw=1&pmid=28423499 #FOAvip Liver fibrosis is a global health problem and its relationship with imidazoline I2 receptor has not been reported. This study aimed to investigate the effects and underlying mechanisms of imidazoline I2 receptor (I2R) inhibitor idazoxan (IDA) on carbon tetrachloride (CCl4)-induced liver fibrosis. In vivo liver fibrosis in mice was induced by intraperitoneally injections of CCl4 for eight weeks, and in vitro studies were performed on activated LX2 cells treated with transforming growth factor-? (TGF-?). Our results showed that IDA significantly improved liver inflammation, ameliorated hepatic stellate cells activation and reduced collagen accumulation by suppressing the pro-fibrogenic signaling of TGF-?/Smad. Further investigation showed that IDA significantly balanced oxidative stress through improving the expressions and activities of anti-oxidant and detoxifying enzymes and activating Nrf2-the key defender against oxidative stress with anti-fibrotic potentials. Even more impressively, knock out of Nrf2 or suppression of Akt by perifosine (PE) eliminated the anti-oxidant and anti-fibrotic effects of IDA in vivo and in vitro, suggesting that Akt/Nrf2 constitutes a critical component of IDA's protective functions. Taken together, IDA exhibits potent effects against liver fibrosis via Akt-Nrf2-Smad2/3 signaling pathway, which suggests that specifically targeting I2R may be a potentially useful therapeutic strategy for liver fibrosis. Twit Text FOAVip Imidazoline I2 receptor inhibitor idazoxan regulates the progression of hepatic fibrosis via Akt-Nrf2-Smad2/3 signaling pathway ????Oncotarget http://www.kidney.de/pget.php?&tw=1&pmid=28423499 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28423499 #FOAvip English Wikipedia <ref>{{Cite pmid|28423499 }}</ref> Imidazoline I2 receptor inhibitor idazoxan regulates the progression of hepatic fibrosis via Akt-Nrf2-Smad2/3 signaling pathway #MMPMID28423499 Xuanfei L ; Hao C ; Zhujun Y ; Yanming L ; Jianping G Oncotarget 2017[Mar]; 8 (13 ): 21015-21030 PMID28423499 show ga Liver fibrosis is a global health problem and its relationship with imidazoline I2 receptor has not been reported. This study aimed to investigate the effects and underlying mechanisms of imidazoline I2 receptor (I2R) inhibitor idazoxan (IDA) on carbon tetrachloride (CCl4)-induced liver fibrosis. In vivo liver fibrosis in mice was induced by intraperitoneally injections of CCl4 for eight weeks, and in vitro studies were performed on activated LX2 cells treated with transforming growth factor-? (TGF-?). Our results showed that IDA significantly improved liver inflammation, ameliorated hepatic stellate cells activation and reduced collagen accumulation by suppressing the pro-fibrogenic signaling of TGF-?/Smad. Further investigation showed that IDA significantly balanced oxidative stress through improving the expressions and activities of anti-oxidant and detoxifying enzymes and activating Nrf2-the key defender against oxidative stress with anti-fibrotic potentials. Even more impressively, knock out of Nrf2 or suppression of Akt by perifosine (PE) eliminated the anti-oxidant and anti-fibrotic effects of IDA in vivo and in vitro, suggesting that Akt/Nrf2 constitutes a critical component of IDA's protective functions. Taken together, IDA exhibits potent effects against liver fibrosis via Akt-Nrf2-Smad2/3 signaling pathway, which suggests that specifically targeting I2R may be a potentially useful therapeutic strategy for liver fibrosis. |Adrenergic alpha-2 Receptor Antagonists/pharmacology [MESH] |Animals [MESH] |Apoptosis/drug effects [MESH] |Carbon Tetrachloride/toxicity [MESH] |Cell Proliferation/drug effects [MESH] |Hepatic Stellate Cells/drug effects/metabolism/*pathology [MESH] |Humans [MESH] |Idazoxan/*pharmacology [MESH] |Imidazoline Receptors/*antagonists & inhibitors [MESH] |Liver Cirrhosis/chemically induced/drug therapy/metabolism/*pathology [MESH] |Mice [MESH] |Mice, Inbred C57BL [MESH] |Mice, Knockout [MESH] |NF-E2-Related Factor 2/*physiology [MESH] |Oxidative Stress/drug effects [MESH] |Proto-Oncogene Proteins c-akt/*metabolism [MESH] |Signal Transduction/drug effects [MESH] |Smad2 Protein/*metabolism [MESH] |Smad3 Protein/*metabolism [MESH]Imidazoline I2 receptor inhibitor idazoxan regulates the progression o(epmc).pdf DeepDyve Pubget Overpricing