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10.1152/ajplung.00195.2011 http://scihub22266oqcxt.onion/10.1152/ajplung.00195.2011 21926265!3233829!21926265     free     free     free Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Am+J+Physiol+Lung+Cell+Mol+Physiol 2011 ; 301 (6): L881-91 Nephropedia Template TP {{tp|p=21926265|t=2011. The PPARgamma ligand rosiglitazone attenuates hypoxia-induced endothelin signaling in vitro and in vivo |pdf=|usr=}}{{21926265}} gab.com Text The PPARgamma ligand rosiglitazone attenuates hypoxia-induced endothelin signaling in vitro and in vivo JO: Am J Physiol Lung Cell Mol Physiol http://www.kidney.de/pget.php?&tw=1&pmid=21926265 #FOAvip Peroxisome proliferator-activated receptor (PPAR) gamma activation attenuates hypoxia-induced pulmonary hypertension (PH) in mice. The current study examined the hypothesis that PPARgamma attenuates hypoxia-induced endothelin-1 (ET-1) signaling to mediate these therapeutic effects. To test this hypothesis, human pulmonary artery endothelial cells (HPAECs) were exposed to normoxia or hypoxia (1% O(2)) for 72 h and treated with or without the PPARgamma ligand rosiglitazone (RSG, 10 muM) during the final 24 h of exposure. HPAEC proliferation was measured with MTT assays or cell counting, and mRNA and protein levels of ET-1 signaling components were determined. To explore the role of hypoxia-activated transcription factors, selected HPAECs were treated with inhibitors of hypoxia-inducible factor (HIF)-1alpha (chetomin) or nuclear factor (NF)-kappaB (caffeic acid phenethyl ester, CAPE). In parallel studies, male C57BL/6 mice were exposed to normoxia (21% O(2)) or hypoxia (10% O(2)) for 3 wk with or without gavage with RSG (10 mg.kg(-1).day(-1)) for the final 10 days of exposure. Hypoxia increased ET-1, endothelin-converting enzyme-1, and endothelin receptor A and B levels in mouse lung and in HPAECs and increased HPAEC proliferation. Treatment with RSG attenuated hypoxia-induced activation of HIF-1alpha, NF-kappaB activation, and ET-1 signaling pathway components. Similarly, treatment with chetomin or CAPE prevented hypoxia-induced increases in HPAEC ET-1 mRNA and protein levels. These findings indicate that PPARgamma activation attenuates a program of hypoxia-induced ET-1 signaling by inhibiting activation of hypoxia-responsive transcription factors. Targeting PPARgamma represents a novel therapeutic strategy to inhibit enhanced ET-1 signaling in PH pathogenesis. Twit Text FOAVip The PPARgamma ligand rosiglitazone attenuates hypoxia-induced endothelin signaling in vitro and in vivo ????Am J Physiol Lung Cell Mol Physiol http://www.kidney.de/pget.php?&tw=1&pmid=21926265 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=21926265 #FOAvip English Wikipedia <ref>{{Cite pmid|21926265}}</ref> The PPARgamma ligand rosiglitazone attenuates hypoxia-induced endothelin signaling in vitro and in vivo #MMPMID21926265 Kang BY; Kleinhenz JM; Murphy TC; Hart CM Am J Physiol Lung Cell Mol Physiol 2011[Dec]; 301 (6): L881-91 PMID21926265show ga Peroxisome proliferator-activated receptor (PPAR) gamma activation attenuates hypoxia-induced pulmonary hypertension (PH) in mice. The current study examined the hypothesis that PPARgamma attenuates hypoxia-induced endothelin-1 (ET-1) signaling to mediate these therapeutic effects. To test this hypothesis, human pulmonary artery endothelial cells (HPAECs) were exposed to normoxia or hypoxia (1% O(2)) for 72 h and treated with or without the PPARgamma ligand rosiglitazone (RSG, 10 muM) during the final 24 h of exposure. HPAEC proliferation was measured with MTT assays or cell counting, and mRNA and protein levels of ET-1 signaling components were determined. To explore the role of hypoxia-activated transcription factors, selected HPAECs were treated with inhibitors of hypoxia-inducible factor (HIF)-1alpha (chetomin) or nuclear factor (NF)-kappaB (caffeic acid phenethyl ester, CAPE). In parallel studies, male C57BL/6 mice were exposed to normoxia (21% O(2)) or hypoxia (10% O(2)) for 3 wk with or without gavage with RSG (10 mg.kg(-1).day(-1)) for the final 10 days of exposure. Hypoxia increased ET-1, endothelin-converting enzyme-1, and endothelin receptor A and B levels in mouse lung and in HPAECs and increased HPAEC proliferation. Treatment with RSG attenuated hypoxia-induced activation of HIF-1alpha, NF-kappaB activation, and ET-1 signaling pathway components. Similarly, treatment with chetomin or CAPE prevented hypoxia-induced increases in HPAEC ET-1 mRNA and protein levels. These findings indicate that PPARgamma activation attenuates a program of hypoxia-induced ET-1 signaling by inhibiting activation of hypoxia-responsive transcription factors. Targeting PPARgamma represents a novel therapeutic strategy to inhibit enhanced ET-1 signaling in PH pathogenesis. |*Signal Transduction[MESH] |Animals[MESH] |Aspartic Acid Endopeptidases/genetics/metabolism[MESH] |Cell Hypoxia[MESH] |Cell Proliferation/drug effects[MESH] |Endothelial Cells/metabolism[MESH] |Endothelin-1/genetics/*metabolism[MESH] |Endothelin-Converting Enzymes[MESH] |Gene Expression[MESH] |Gene Expression Regulation/drug effects[MESH] |Humans[MESH] |Hypoxia[MESH] |Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism[MESH] |Lung/metabolism/pathology[MESH] |Male[MESH] |Metalloendopeptidases/genetics/metabolism[MESH] |Mice[MESH] |Mice, Inbred C57BL[MESH] |NF-kappa B/genetics/metabolism[MESH] |PPAR gamma/*agonists[MESH] |Pulmonary Artery/pathology[MESH] |Receptor, Endothelin A/genetics/metabolism[MESH] |Receptor, Endothelin B/genetics/metabolism[MESH] |Rosiglitazone[MESH]The PPARgamma ligand rosiglitazone attenuates hypoxia-induced endothel(epmc).pdf DeepDyve Pubget Overpricing