Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 267.2 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\27827416
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Sci+Rep
2016 ; 6
(ä): 36533
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Obesity-induced kidney injury is attenuated by amelioration of aberrant PHD2
activation in proximal tubules
#MMPMID27827416
Futatsugi K
; Tokuyama H
; Shibata S
; Naitoh M
; Kanda T
; Minakuchi H
; Yamaguchi S
; Hayashi K
; Minamishima YA
; Yanagita M
; Wakino S
; Itoh H
Sci Rep
2016[Nov]; 6
(ä): 36533
PMID27827416
show ga
The involvement of tissue ischemia in obesity-induced kidney injury remains to be
elucidated. Compared with low fat diet (LFD)-mice, high fat diet (HFD)-fed mice
became obese with tubular enlargement, glomerulomegaly and peritubular capillary
rarefaction, and exhibited both tubular and glomerular damages. In HFD-fed mice,
despite the increase in renal pimonidazole-positive areas, the expressions of the
hypoxia-responsive genes such as Prolyl-hydroxylase PHD2, a dominant oxygen
sensor, and VEGFA were unchanged indicating impaired hypoxic response. Tamoxifen
inducible proximal tubules (PT)-specific Phd2 knockout (Phd2-cKO) mice and their
littermate control mice (Control) were created and fed HFD or LFD. Control mice
on HFD (Control HFD) exhibited renal damages and renal ischemia with impaired
hypoxic response compared with those on LFD. After tamoxifen treatment, HFD-fed
knockout mice (Phd2-cKO HFD) had increased peritubular capillaries and the
increased expressions of hypoxia responsive genes compared to Control HFD mice.
Phd2-cKO HFD also exhibited the mitigation of tubular damages, albuminuria and
glomerulomegaly. In human PT cells, the increased expressions of
hypoxia-inducible genes in hypoxic condition were attenuated by free fatty acids.
Thus, aberrant hypoxic responses due to dysfunction of PHD2 caused both
glomerular and tubular damages in HFD-induced obese mice. Phd2-inactivation
provides a novel strategy against obesity-induced kidney injury.