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10.1681/ASN.2016080841 http://scihub22266oqcxt.onion/10.1681/ASN.2016080841 C5491283!5491283!28220029     free     free     free Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Am+Soc+Nephrol 2017 ; 28 (7): 2133-43 Nephropedia Template TP {{tp|p=28220029|t=2017. A Novel Inhibitor of Homeodomain Interacting Protein Kinase 2 Mitigates Kidney Fibrosis through Inhibition of the TGF-?1/Smad3 Pathway |pdf=|usr=}}{{28220029}} gab.com Text A Novel Inhibitor of Homeodomain Interacting Protein Kinase 2 Mitigates Kidney Fibrosis through Inhibition of the TGF- 1/Smad3 Pathway JO: J Am Soc Nephrol http://www.kidney.de/pget.php?&tw=1&pmid=28220029 #FOAvip Homeodomain interacting protein kinase 2 (HIPK2) is a critical regulator of multiple profibrotic pathways, including that of TGF-?1/Smad3. Genetic ablation of HIPK2 was shown previously to significantly reduce renal fibrosis in the experimental unilateral ureteral obstruction model and Tg26 mice, a model of HIV-associated nephropathy. To develop specific pharmacologic inhibitors of HIPK2 for antifibrotic therapy, we designed and synthesized small molecule inhibitor compounds on the basis of the predicted structure of HIPK2. Among these compounds, we identified one, BT173, that strongly inhibited the ability of HIPK2 to potentiate the downstream transcriptional activity of Smad3 in kidney tubular cells. Notably, binding of BT173 to HIPK2 did not inhibit HIPK2 kinase activity but rather, interfered allosterically with the ability of HIPK2 to associate with Smad3. In vitro, treatment with BT173 inhibited TGF-?1?induced Smad3 phosphorylation and Smad3 target gene expression in human renal tubular epithelial cells. In vivo, administration of BT173 decreased Smad3 phosphorylation and mitigated renal fibrosis and deposition of extracellular matrix in unilateral ureteral obstruction and Tg26 mouse models of renal fibrosis. Our data indicate that BT173 is a novel HIPK2 inhibitor that attenuates renal fibrosis through suppression of the TGF-?1/Smad3 pathway and may be developed as an antifibrotic therapy in patients with kidney disease. Twit Text FOAVip A Novel Inhibitor of Homeodomain Interacting Protein Kinase 2 Mitigates Kidney Fibrosis through Inhibition of the TGF- 1/Smad3 Pathway ????J Am Soc Nephrol http://www.kidney.de/pget.php?&tw=1&pmid=28220029 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28220029 #FOAvip English Wikipedia <ref>{{Cite pmid|28220029}}</ref> A Novel Inhibitor of Homeodomain Interacting Protein Kinase 2 Mitigates Kidney Fibrosis through Inhibition of the TGF-?1/Smad3 Pathway #MMPMID28220029 Liu R; Das B; Xiao W; Li Z; Li H; Lee K; He JC J Am Soc Nephrol 2017[Jul]; 28 (7): 2133-43 PMID28220029show ga Homeodomain interacting protein kinase 2 (HIPK2) is a critical regulator of multiple profibrotic pathways, including that of TGF-?1/Smad3. Genetic ablation of HIPK2 was shown previously to significantly reduce renal fibrosis in the experimental unilateral ureteral obstruction model and Tg26 mice, a model of HIV-associated nephropathy. To develop specific pharmacologic inhibitors of HIPK2 for antifibrotic therapy, we designed and synthesized small molecule inhibitor compounds on the basis of the predicted structure of HIPK2. Among these compounds, we identified one, BT173, that strongly inhibited the ability of HIPK2 to potentiate the downstream transcriptional activity of Smad3 in kidney tubular cells. Notably, binding of BT173 to HIPK2 did not inhibit HIPK2 kinase activity but rather, interfered allosterically with the ability of HIPK2 to associate with Smad3. In vitro, treatment with BT173 inhibited TGF-?1?induced Smad3 phosphorylation and Smad3 target gene expression in human renal tubular epithelial cells. In vivo, administration of BT173 decreased Smad3 phosphorylation and mitigated renal fibrosis and deposition of extracellular matrix in unilateral ureteral obstruction and Tg26 mouse models of renal fibrosis. Our data indicate that BT173 is a novel HIPK2 inhibitor that attenuates renal fibrosis through suppression of the TGF-?1/Smad3 pathway and may be developed as an antifibrotic therapy in patients with kidney disease. äA Novel Inhibitor of Homeodomain Interacting Protein Kinase 2 Mitigate(epmc).pdf DeepDyve Pubget Overpricing