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10.1038/s41598-019-51343-1 http://scihub22266oqcxt.onion/10.1038/s41598-019-51343-1 31611596!6791873!31611596     free     free     free Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 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\31611596.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Sci+Rep 2019 ; 9 (1): 14754 Nephropedia Template TP {{tp|p=31611596|t=2019. Hypoxia-inducible factor-1alpha is the therapeutic target of the SGLT2 inhibitor for diabetic nephropathy |pdf=|usr=}}{{31611596}} gab.com Text Hypoxia-inducible factor-1alpha is the therapeutic target of the SGLT2 inhibitor for diabetic nephropathy JO: Sci Rep http://www.kidney.de/pget.php?&tw=1&pmid=31611596 #FOAvip Previous studies have demonstrated intrarenal hypoxia in patients with diabetes. Hypoxia-inducible factor (HIF)-1 plays an important role in hypoxia-induced tubulointerstitial fibrosis. Recent clinical trials have confirmed the renoprotective action of SGLT2 inhibitors in diabetic nephropathy. We explored the effects of an SGLT2 inhibitor, luseogliflozin on HIF-1alpha expression in human renal proximal tubular epithelial cells (HRPTECs). Luseogliflozin significantly inhibited hypoxia-induced HIF-1alpha protein expression in HRPTECs. In addition, luseogliflozin inhibited hypoxia-induced the expression of the HIF-1alpha target genes PAI-1, VEGF, GLUT1, HK2 and PKM. Although luseogliflozin increased phosphorylated-AMP-activated protein kinase alpha (p-AMPKalpha) levels, the AMPK activator AICAR did not changed hypoxia-induced HIF-1alpha expression. Luseogliflozin suppressed the oxygen consumption rate in HRPTECs, and subsequently decreased hypoxia-sensitive dye, pimonidazole staining under hypoxia, suggesting that luseogliflozin promoted the degradation of HIF-1alpha protein by redistribution of intracellular oxygen. To confirm the inhibitory effect of luseogliflozin on hypoxia-induced HIF-1alpha protein in vivo, we treated male diabetic db/db mice with luseogliflozin for 8 to 16 weeks. Luseogliflozin attenuated cortical tubular HIF-1alpha expression, tubular injury and interstitial fibronectin in db/db mice. Together, luseogliflozin inhibits hypoxia-induced HIF-1alpha accumulation by suppressing mitochondrial oxygen consumption. The SGLT2 inhibitors may protect diabetic kidneys by therapeutically targeting HIF-1alpha protein. Twit Text FOAVip Hypoxia-inducible factor-1alpha is the therapeutic target of the SGLT2 inhibitor for diabetic nephropathy ????Sci Rep http://www.kidney.de/pget.php?&tw=1&pmid=31611596 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=31611596 #FOAvip English Wikipedia <ref>{{Cite pmid|31611596}}</ref> Hypoxia-inducible factor-1alpha is the therapeutic target of the SGLT2 inhibitor for diabetic nephropathy #MMPMID31611596 Bessho R; Takiyama Y; Takiyama T; Kitsunai H; Takeda Y; Sakagami H; Ota T Sci Rep 2019[Oct]; 9 (1): 14754 PMID31611596show ga Previous studies have demonstrated intrarenal hypoxia in patients with diabetes. Hypoxia-inducible factor (HIF)-1 plays an important role in hypoxia-induced tubulointerstitial fibrosis. Recent clinical trials have confirmed the renoprotective action of SGLT2 inhibitors in diabetic nephropathy. We explored the effects of an SGLT2 inhibitor, luseogliflozin on HIF-1alpha expression in human renal proximal tubular epithelial cells (HRPTECs). Luseogliflozin significantly inhibited hypoxia-induced HIF-1alpha protein expression in HRPTECs. In addition, luseogliflozin inhibited hypoxia-induced the expression of the HIF-1alpha target genes PAI-1, VEGF, GLUT1, HK2 and PKM. Although luseogliflozin increased phosphorylated-AMP-activated protein kinase alpha (p-AMPKalpha) levels, the AMPK activator AICAR did not changed hypoxia-induced HIF-1alpha expression. Luseogliflozin suppressed the oxygen consumption rate in HRPTECs, and subsequently decreased hypoxia-sensitive dye, pimonidazole staining under hypoxia, suggesting that luseogliflozin promoted the degradation of HIF-1alpha protein by redistribution of intracellular oxygen. To confirm the inhibitory effect of luseogliflozin on hypoxia-induced HIF-1alpha protein in vivo, we treated male diabetic db/db mice with luseogliflozin for 8 to 16 weeks. Luseogliflozin attenuated cortical tubular HIF-1alpha expression, tubular injury and interstitial fibronectin in db/db mice. Together, luseogliflozin inhibits hypoxia-induced HIF-1alpha accumulation by suppressing mitochondrial oxygen consumption. The SGLT2 inhibitors may protect diabetic kidneys by therapeutically targeting HIF-1alpha protein. |Animals[MESH] |Cell Hypoxia/drug effects[MESH] |Diabetes Mellitus/*drug therapy/metabolism[MESH] |Diabetic Nephropathies/*drug therapy/metabolism[MESH] |Hypoglycemic Agents/*therapeutic use[MESH] |Hypoxia-Inducible Factor 1, alpha Subunit/metabolism[MESH] |Male[MESH] |Mice[MESH] |Mice, Inbred C57BL[MESH] |Oxygen/metabolism[MESH] |Sodium-Glucose Transporter 2 Inhibitors/*therapeutic use[MESH]Hypoxia-inducible factor-1alpha is the therapeutic target of the SGLT2(epmc).pdf DeepDyve Pubget Overpricing