Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26647385
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 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\26647385
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Diabetes
2016 ; 65
(3
): 633-46
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Restoration of Nrf2 Signaling Normalizes the Regenerative Niche
#MMPMID26647385
Soares MA
; Cohen OD
; Low YC
; Sartor RA
; Ellison T
; Anil U
; Anzai L
; Chang JB
; Saadeh PB
; Rabbani PS
; Ceradini DJ
Diabetes
2016[Mar]; 65
(3
): 633-46
PMID26647385
show ga
Chronic hyperglycemia impairs intracellular redox homeostasis and contributes to
impaired diabetic tissue regeneration. The Keap1/Nrf2 pathway is a critical
regulator of the endogenous antioxidant response system, and its dysfunction has
been implicated in numerous pathologies. Here we characterize the effect of
chronic hyperglycemia on Nrf2 signaling within a diabetic cutaneous regeneration
model. We characterized the effects of chronic hyperglycemia on the Keap1/Nrf2
pathway within models of diabetic cutaneous wound regeneration. We assessed
reactive oxygen species (ROS) production and antioxidant gene expression
following alterations in the Nrf2 suppressor Keap1 and the subsequent changes in
Nrf2 signaling. We also developed a topical small interfering RNA (siRNA)-based
therapy to restore redox homeostasis within diabetic wounds. Western blotting
demonstrated that chronic hyperglycemia-associated oxidative stress inhibits
nuclear translocation of Nrf2 and impairs activation of antioxidant genes, thus
contributing to ROS accumulation. Keap1 inhibition increased Nrf2 nuclear
translocation, increased antioxidant gene expression, and reduced ROS production
to normoglycemic levels, both in vitro and in vivo. Topical siKeap1 therapy
resulted in improved regenerative capacity of diabetic wounds and accelerated
closure. We report that chronic hyperglycemia weakens the endogenous antioxidant
response, and the consequences of this defect are manifested by intracellular
redox dysregulation, which can be restored by Keap1 inhibition. Targeted
siRNA-based therapy represents a novel, efficacious strategy to reestablish redox
homeostasis and accelerate diabetic cutaneous tissue regeneration.
|Adaptor Proteins, Signal Transducing/genetics/*metabolism
[MESH]
free
free
free
