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10.1111/bph.12837 http://scihub22266oqcxt.onion/10.1111/bph.12837 C4253459!4253459 !25041068     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 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 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\25041068 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Br+J+Pharmacol 2014 ; 171 (22 ): 5113-26 Nephropedia Template TP {{tp|p=25041068 |t=2014. Ursodeoxycholyl lysophosphatidylethanolamide attenuates hepatofibrogenesis by impairment of TGF-?1/Smad2/3 signalling |pdf=|usr=}}{{25041068 }} gab.com Text Ursodeoxycholyl lysophosphatidylethanolamide attenuates hepatofibrogenesis by impairment of TGF- 1/Smad2/3 signalling JO: Br J Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=25041068 #FOAvip BACKGROUND AND PURPOSE: Chronic hepatic inflammation results in liver fibrosis. As effective anti-fibrogenic agents are lacking, we investigated ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE), a synthetic bile acid-phospholipid conjugate with anti-inflammatory and anti-apoptotic properties for tis effects on hepatic fibrogenesis. EXPERIMENTAL APPROACH: To stimulate fibrogenesis, LX2 hepatic stellate cells were cultured with conditioned medium from CL48 liver cells after exposure to stress-inducing conditions - methionine-choline-deficient (MCD) medium or TNF?/cycloheximide (CHX) - with or without UDCA-LPE preincubation. Anti-fibrogenic effects of UDCA-LPE were further studied in CL48 and LX2 cells and in primary human hepatic stellate cells (HHStec) directly exposed to TGF-?1. To test UDCA-LPE?in vivo, C57BL/6 mice were fed a MCD diet for 11 weeks followed by 30?mg·kg(-1) UDCA-LPE 3× per week for 2.5 weeks. KEY RESULTS: Expression of ?-smooth muscle actin (?-SMA), ?1-collagen, vimentin and TGF-?1 was down-regulated by up to 93% by UDCA-LPE in LX-2 cells cultured with conditioned medium. Also, UDCA-LPE inhibited Smad3 phosphorylation in CL48 cells incubated with MCD medium or TNF?/CHX and in LX2 cells exposed to conditioned medium. UDCA-LPE also decreased phosphorylated Smad3 and Smad2 directly induced by TGF-?1. Inhibition of TGF-?1/Smad2/3 signalling with down-regulation of target genes was confirmed in HHStec. In vivo, UDCA-LPE decreased hepatic ?-SMA, ?1-collagen and TGF-?1 expression and markedly lowered ?-SMA protein and collagen deposition in MCD mice. CONCLUSIONS AND IMPLICATIONS: By blocking TGF-?1/Smad2/3 signalling, UDCA-LPE suppressed key mediators of hepatic fibrogenesis. Thus, UDCA-LPE could be suitable for prevention of fibrotic progression of chronic liver disease. Twit Text FOAVip Ursodeoxycholyl lysophosphatidylethanolamide attenuates hepatofibrogenesis by impairment of TGF- 1/Smad2/3 signalling ????Br J Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=25041068 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25041068 #FOAvip English Wikipedia <ref>{{Cite pmid|25041068 }}</ref> Ursodeoxycholyl lysophosphatidylethanolamide attenuates hepatofibrogenesis by impairment of TGF-?1/Smad2/3 signalling #MMPMID25041068 Pathil A ; Mueller J ; Ludwig JM ; Wang J ; Warth A ; Chamulitrat W ; Stremmel W Br J Pharmacol 2014[Nov]; 171 (22 ): 5113-26 PMID25041068 show ga BACKGROUND AND PURPOSE: Chronic hepatic inflammation results in liver fibrosis. As effective anti-fibrogenic agents are lacking, we investigated ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE), a synthetic bile acid-phospholipid conjugate with anti-inflammatory and anti-apoptotic properties for tis effects on hepatic fibrogenesis. EXPERIMENTAL APPROACH: To stimulate fibrogenesis, LX2 hepatic stellate cells were cultured with conditioned medium from CL48 liver cells after exposure to stress-inducing conditions - methionine-choline-deficient (MCD) medium or TNF?/cycloheximide (CHX) - with or without UDCA-LPE preincubation. Anti-fibrogenic effects of UDCA-LPE were further studied in CL48 and LX2 cells and in primary human hepatic stellate cells (HHStec) directly exposed to TGF-?1. To test UDCA-LPE?in vivo, C57BL/6 mice were fed a MCD diet for 11 weeks followed by 30?mg·kg(-1) UDCA-LPE 3× per week for 2.5 weeks. KEY RESULTS: Expression of ?-smooth muscle actin (?-SMA), ?1-collagen, vimentin and TGF-?1 was down-regulated by up to 93% by UDCA-LPE in LX-2 cells cultured with conditioned medium. Also, UDCA-LPE inhibited Smad3 phosphorylation in CL48 cells incubated with MCD medium or TNF?/CHX and in LX2 cells exposed to conditioned medium. UDCA-LPE also decreased phosphorylated Smad3 and Smad2 directly induced by TGF-?1. Inhibition of TGF-?1/Smad2/3 signalling with down-regulation of target genes was confirmed in HHStec. In vivo, UDCA-LPE decreased hepatic ?-SMA, ?1-collagen and TGF-?1 expression and markedly lowered ?-SMA protein and collagen deposition in MCD mice. CONCLUSIONS AND IMPLICATIONS: By blocking TGF-?1/Smad2/3 signalling, UDCA-LPE suppressed key mediators of hepatic fibrogenesis. Thus, UDCA-LPE could be suitable for prevention of fibrotic progression of chronic liver disease. |Actins/genetics [MESH] |Animals [MESH] |Anti-Inflammatory Agents/chemistry/*pharmacology/therapeutic use [MESH] |Cell Line [MESH] |Collagen Type I/genetics [MESH] |Gene Expression Regulation/drug effects [MESH] |Hepatic Stellate Cells/drug effects/metabolism [MESH] |Humans [MESH] |Liver Cirrhosis/drug therapy/genetics/*metabolism [MESH] |Lysophospholipids/*pharmacology/therapeutic use [MESH] |Male [MESH] |Mice, Inbred C57BL [MESH] |Signal Transduction [MESH] |Smad2 Protein/*metabolism [MESH] |Smad3 Protein/*metabolism [MESH] |Transforming Growth Factor beta1/genetics/*metabolism [MESH] |Ursodeoxycholic Acid/*analogs & derivatives/pharmacology/therapeutic use [MESH]Ursodeoxycholyl lysophosphatidylethanolamide attenuates hepatofibrogen(epmc).pdf DeepDyve Pubget Overpricing