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10.1111/vop.12331 http://scihub22266oqcxt.onion/10.1111/vop.12331 C4865451!4865451!26559782     free     free     free Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Vet+Ophthalmol 2016 ; 19 (6): 480-7 Nephropedia Template TP {{tp|p=26559782|t=2016. Molecular Mechanisms of Suberoylanilide Hydroxamic Acid (SAHA) in the Inhibition of TGF-?1 Mediated Canine Corneal Fibrosis |pdf=|usr=}}{{26559782}} gab.com Text Molecular Mechanisms of Suberoylanilide Hydroxamic Acid (SAHA) in the Inhibition of TGF- 1 Mediated Canine Corneal Fibrosis JO: Vet Ophthalmol http://www.kidney.de/pget.php?&tw=1&pmid=26559782 #FOAvip Objective: To investigate molecular mechanisms mediating anti-fibrotic effect of SAHA in the canine cornea using an in vitro model. We hypothesized that SAHA attenuates corneal fibrosis by modulating Smad-dependent and, to a lesser extent, Smad-independent signaling pathways activated by TGF-?1, as well as matrix metalloproteinase (MMP) activity. Methods: Cultured canine corneal fibroblasts (CCF) were incubated in the presence/absence of TGF-?1 (5ng/ml) and SAHA (2.5?M) for 24hrs. Western blot analysis was used to quantify non-phosphorylated and phosphorylated isoforms of Smad2/3, p38 MAP kinase (MAPK), ERK1/2 and JNK1. Real-time PCR and zymography were utilized to quantify MMP1, MMP2, MMP8 and MMP9 mRNA expression and MMP2 and MMP9 protein activity, respectively. Results: TGF-?1 treatment caused a significant increase in phospho-Smad2/3 and phospho-p38 MAPK. SAHA treatment reduced TGF-?1-induced phosphorylation of Smad2/3 but not of p38 MAPK. TGF-?1 did not modulate the phosphorylation of ERK1/2 or JNK1. SAHA caused a significant reduction in phospho-ERK1/2 expression regardless of concurrent TGF-?1 treatment. Neither SAHA alone nor in combination with TGF-?1 altered phospho-JNK1 expression. TGF-?1 significantly increased MMP1 and MMP9 mRNA expression but did not alter MMP2 mRNA. SAHA treatment attenuated TGF-?1-induced MMP9 mRNA expression while significantly enhancing TGF-?1-induced MMP1 mRNA expression. Zymography detected reduced expression of MMP2 and MMP9 proteins in untreated control CCF. TGF-?1 treatment did not alter their expression but SAHA treatment +/?TGF-?1 significantly increased MMP2 and MMP9 protein expression. Conclusions: The corneal anti-fibrotic effects of SAHA involve multiple mechanisms including modulation of canonical and non-canonical components of TGF-?1 intracellular signaling and MMP activity. Twit Text FOAVip Molecular Mechanisms of Suberoylanilide Hydroxamic Acid (SAHA) in the Inhibition of TGF- 1 Mediated Canine Corneal Fibrosis ????Vet Ophthalmol http://www.kidney.de/pget.php?&tw=1&pmid=26559782 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26559782 #FOAvip English Wikipedia <ref>{{Cite pmid|26559782}}</ref> Molecular Mechanisms of Suberoylanilide Hydroxamic Acid (SAHA) in the Inhibition of TGF-?1 Mediated Canine Corneal Fibrosis #MMPMID26559782 Gronkiewicz KM; Giuliano EA; Sharma A; Mohan RR Vet Ophthalmol 2016[Nov]; 19 (6): 480-7 PMID26559782show ga Objective: To investigate molecular mechanisms mediating anti-fibrotic effect of SAHA in the canine cornea using an in vitro model. We hypothesized that SAHA attenuates corneal fibrosis by modulating Smad-dependent and, to a lesser extent, Smad-independent signaling pathways activated by TGF-?1, as well as matrix metalloproteinase (MMP) activity. Methods: Cultured canine corneal fibroblasts (CCF) were incubated in the presence/absence of TGF-?1 (5ng/ml) and SAHA (2.5?M) for 24hrs. Western blot analysis was used to quantify non-phosphorylated and phosphorylated isoforms of Smad2/3, p38 MAP kinase (MAPK), ERK1/2 and JNK1. Real-time PCR and zymography were utilized to quantify MMP1, MMP2, MMP8 and MMP9 mRNA expression and MMP2 and MMP9 protein activity, respectively. Results: TGF-?1 treatment caused a significant increase in phospho-Smad2/3 and phospho-p38 MAPK. SAHA treatment reduced TGF-?1-induced phosphorylation of Smad2/3 but not of p38 MAPK. TGF-?1 did not modulate the phosphorylation of ERK1/2 or JNK1. SAHA caused a significant reduction in phospho-ERK1/2 expression regardless of concurrent TGF-?1 treatment. Neither SAHA alone nor in combination with TGF-?1 altered phospho-JNK1 expression. TGF-?1 significantly increased MMP1 and MMP9 mRNA expression but did not alter MMP2 mRNA. SAHA treatment attenuated TGF-?1-induced MMP9 mRNA expression while significantly enhancing TGF-?1-induced MMP1 mRNA expression. Zymography detected reduced expression of MMP2 and MMP9 proteins in untreated control CCF. TGF-?1 treatment did not alter their expression but SAHA treatment +/?TGF-?1 significantly increased MMP2 and MMP9 protein expression. Conclusions: The corneal anti-fibrotic effects of SAHA involve multiple mechanisms including modulation of canonical and non-canonical components of TGF-?1 intracellular signaling and MMP activity. äMolecular Mechanisms of Suberoylanilide Hydroxamic Acid (SAHA) in the (epmc).pdf DeepDyve Pubget Overpricing