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10.3389/fphar.2018.00738 http://scihub22266oqcxt.onion/10.3389/fphar.2018.00738 C6048361!6048361 !30042678     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 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\30042678 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Front+Pharmacol 2018 ; 9 (ä): 738 Nephropedia Template TP {{tp|p=30042678 |t=2018. Casein Kinase 1?/? Inhibitor, PF670462 Attenuates the Fibrogenic Effects of Transforming Growth Factor-? in Pulmonary Fibrosis |pdf=|usr=}}{{30042678 }} gab.com Text Casein Kinase 1 / Inhibitor, PF670462 Attenuates the Fibrogenic Effects of Transforming Growth Factor- in Pulmonary Fibrosis JO: Front Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=30042678 #FOAvip Transforming growth factor-beta (TGF-?) is a major mediator of fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). However, therapeutic global inhibition of TGF-? is limited by unwanted immunosuppression and mitral valve defects. We performed an extensive literature search to uncover a little-known connection between TGF-? signaling and casein kinase (CK) activity. We have examined the abundance of CK1 delta and epsilon (CK1?/?) in lung tissue from IPF patients and non-diseased controls, and investigated whether inhibition of CK1?/? with PF670462 inhibits pulmonary fibrosis. CK1?/? levels in lung tissue from IPF patients and non-diseased controls were assessed by immunohistochemistry. Anti-fibrotic effects of the CK1?/? inhibitor PF670462 were assessed in pre-clinical models, including acute and chronic bleomycin mouse models and in vitro experiments on spheroids made from primary human lung fibroblast cells from IPF and control donors, and human A549 alveolar-like adenocarcinoma-derived epithelial cells. Increased expression of CK1? and ? in IPF lungs compared to non-diseased controls was accompanied by increased levels of the product, phospho-period 2. In vitro, PF670462 prevented TGF-?-induced epithelial-mesenchymal transition. The stiffness of IPF-derived spheroids was reduced by PF670462 and TGF-?-induced fibrogenic gene expression was inhibited. The CK1?/? inhibitor PF670462 administered systemically or locally by inhalation prevented both acute and chronic bleomycin-induced pulmonary fibrosis in mice. PF670462 administered in a 'therapeutic' regimen (day 7 onward) prevented bleomycin-induced lung collagen accumulation. Elevated expression and activity of CK1 ? and ? in IPF and anti-fibrogenic effects of the dual CK1?/? inhibitor, PF670462, support CK1?/? as novel therapeutic targets for IPF. Twit Text FOAVip Casein Kinase 1 / Inhibitor, PF670462 Attenuates the Fibrogenic Effects of Transforming Growth Factor- in Pulmonary Fibrosis ????Front Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=30042678 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=30042678 #FOAvip English Wikipedia <ref>{{Cite pmid|30042678 }}</ref> Casein Kinase 1?/? Inhibitor, PF670462 Attenuates the Fibrogenic Effects of Transforming Growth Factor-? in Pulmonary Fibrosis #MMPMID30042678 Keenan CR ; Langenbach SY ; Jativa F ; Harris T ; Li M ; Chen Q ; Xia Y ; Gao B ; Schuliga MJ ; Jaffar J ; Prodanovic D ; Tu Y ; Berhan A ; Lee PVS ; Westall GP ; Stewart AG Front Pharmacol 2018[]; 9 (ä): 738 PMID30042678 show ga Transforming growth factor-beta (TGF-?) is a major mediator of fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). However, therapeutic global inhibition of TGF-? is limited by unwanted immunosuppression and mitral valve defects. We performed an extensive literature search to uncover a little-known connection between TGF-? signaling and casein kinase (CK) activity. We have examined the abundance of CK1 delta and epsilon (CK1?/?) in lung tissue from IPF patients and non-diseased controls, and investigated whether inhibition of CK1?/? with PF670462 inhibits pulmonary fibrosis. CK1?/? levels in lung tissue from IPF patients and non-diseased controls were assessed by immunohistochemistry. Anti-fibrotic effects of the CK1?/? inhibitor PF670462 were assessed in pre-clinical models, including acute and chronic bleomycin mouse models and in vitro experiments on spheroids made from primary human lung fibroblast cells from IPF and control donors, and human A549 alveolar-like adenocarcinoma-derived epithelial cells. Increased expression of CK1? and ? in IPF lungs compared to non-diseased controls was accompanied by increased levels of the product, phospho-period 2. In vitro, PF670462 prevented TGF-?-induced epithelial-mesenchymal transition. The stiffness of IPF-derived spheroids was reduced by PF670462 and TGF-?-induced fibrogenic gene expression was inhibited. The CK1?/? inhibitor PF670462 administered systemically or locally by inhalation prevented both acute and chronic bleomycin-induced pulmonary fibrosis in mice. PF670462 administered in a 'therapeutic' regimen (day 7 onward) prevented bleomycin-induced lung collagen accumulation. Elevated expression and activity of CK1 ? and ? in IPF and anti-fibrogenic effects of the dual CK1?/? inhibitor, PF670462, support CK1?/? as novel therapeutic targets for IPF. äCasein Kinase 1?/? Inhibitor, PF670462 Attenuates the Fibrogenic Effec(epmc).pdf DeepDyve Pubget Overpricing