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2017 ; 23
(ä): 2816-2824
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Silencing of TRB3 Ameliorates Diabetic Tubule Interstitial Nephropathy via
PI3K/AKT Signaling in Rats
#MMPMID28600485
Ma Y
; Chen F
; Yang S
; Duan Y
; Sun Z
; Shi J
Med Sci Monit
2017[Jun]; 23
(ä): 2816-2824
PMID28600485
show ga
BACKGROUND Nephropathy, a chronic progressive kidney disease often characterized
by glomeruli scarring and sclerosis, is a major complication of diabetes
mellitus. Development of nephropathologic lesions has been shown to be associated
with suppressed AKT phosphorylation and elevated level of apoptosis. Moreover, it
has been established that the TRB3 gene is capable of inhibiting AKT
phosphorylation and promoting apoptosis. MATERIAL AND METHODS In this study, we
injected TRB3 siRNA into Wistar rats with type 1 diabetes, and monitored
development of nephropathy in the rats. Urinary albumin excretion and serum
creatinine were used as primary indicators, and nephritic histology was also
examined. We also measured the serum level of pro-inflammatory cytokines collagen
expression, and phosphorylation of PI3K and AKT proteins in the kidneys. RESULTS
By silencing the TRB3 gene with siRNA, diabetic-induced nephropathy symptoms were
alleviated, such as increased serum creatinine level and urinary albumin
secretion. Additionally, histological examination showed lower levels of
nephropathic lesions, and samples of the kidneys showed less accumulation of
collagen proteins. Levels of serum cytokines, including TNF-?, IL-1?, and IL-6,
were also lowered, whereas phosphorylation levels of PI3K and AKT were increased.
In summary, TRB3 silencing in diabetic rats had a significant ameliorative effect
on their nephropathy. CONCLUSIONS Silencing of TRB3 has a significant
ameliorative effect on diabetic nephropathy in rats.