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10.1172/JCI80467 http://scihub22266oqcxt.onion/10.1172/JCI80467 C4497763!4497763!25961459     free     free     free Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Clin+Invest 2015 ; 125 (6): 2399-412 Nephropedia Template TP {{tp|p=25961459|t=2015. Macrophage migration inhibitory factor promotes cyst growth in polycystic kidney disease |pdf=|usr=}}{{25961459}} gab.com Text Macrophage migration inhibitory factor promotes cyst growth in polycystic kidney disease JO: J Clin Invest http://www.kidney.de/pget.php?&tw=1&pmid=25961459 #FOAvip Autosomal dominant polycystic kidney disease (ADPKD) is characterized by renal cyst formation, inflammation, and fibrosis. Macrophages infiltrate cystic kidneys, but the role of these and other inflammatory factors in disease progression are poorly understood. Here, we identified macrophage migration inhibitory factor (MIF) as an important regulator of cyst growth in ADPKD. MIF was upregulated in cyst-lining epithelial cells in polycystin-1?deficient murine kidneys and accumulated in cyst fluid of human ADPKD kidneys. MIF promoted cystic epithelial cell proliferation by activating ERK, mTOR, and Rb/E2F pathways and by increasing glucose uptake and ATP production, which inhibited AMP-activated protein kinase signaling. MIF also regulated cystic renal epithelial cell apoptosis through p53-dependent signaling. In polycystin-1?deficient mice, MIF was required for recruitment and retention of renal macrophages, which promoted cyst expansion, and Mif deletion or pharmacologic inhibition delayed cyst growth in multiple murine ADPKD models. MIF-dependent macrophage recruitment was associated with upregulation of monocyte chemotactic protein 1 (MCP-1) and inflammatory cytokine TNF-?. TNF-? induced MIF expression, and MIF subsequently exacerbated TNF-? expression in renal epithelial cells, suggesting a positive feedback loop between TNF-? and MIF during cyst development. Our study indicates MIF is a central and upstream regulator of ADPKD pathogenesis and provides a rationale for further exploration of MIF as a therapeutic target for ADPKD. Twit Text FOAVip Macrophage migration inhibitory factor promotes cyst growth in polycystic kidney disease ????J Clin Invest http://www.kidney.de/pget.php?&tw=1&pmid=25961459 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25961459 #FOAvip English Wikipedia <ref>{{Cite pmid|25961459}}</ref> Macrophage migration inhibitory factor promotes cyst growth in polycystic kidney disease #MMPMID25961459 Chen L; Zhou X; Fan LX; Yao Y; Swenson-Fields KI; Gadjeva M; Wallace DP; Peters DJ; Yu A; Grantham JJ; Li X J Clin Invest 2015[Jun]; 125 (6): 2399-412 PMID25961459show ga Autosomal dominant polycystic kidney disease (ADPKD) is characterized by renal cyst formation, inflammation, and fibrosis. Macrophages infiltrate cystic kidneys, but the role of these and other inflammatory factors in disease progression are poorly understood. Here, we identified macrophage migration inhibitory factor (MIF) as an important regulator of cyst growth in ADPKD. MIF was upregulated in cyst-lining epithelial cells in polycystin-1?deficient murine kidneys and accumulated in cyst fluid of human ADPKD kidneys. MIF promoted cystic epithelial cell proliferation by activating ERK, mTOR, and Rb/E2F pathways and by increasing glucose uptake and ATP production, which inhibited AMP-activated protein kinase signaling. MIF also regulated cystic renal epithelial cell apoptosis through p53-dependent signaling. In polycystin-1?deficient mice, MIF was required for recruitment and retention of renal macrophages, which promoted cyst expansion, and Mif deletion or pharmacologic inhibition delayed cyst growth in multiple murine ADPKD models. MIF-dependent macrophage recruitment was associated with upregulation of monocyte chemotactic protein 1 (MCP-1) and inflammatory cytokine TNF-?. TNF-? induced MIF expression, and MIF subsequently exacerbated TNF-? expression in renal epithelial cells, suggesting a positive feedback loop between TNF-? and MIF during cyst development. Our study indicates MIF is a central and upstream regulator of ADPKD pathogenesis and provides a rationale for further exploration of MIF as a therapeutic target for ADPKD. äMacrophage migration inhibitory factor promotes cyst growth in polycys(epmc).pdf DeepDyve Pubget Overpricing