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2015 ; 12
(1
): 45-54
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Klotho gene delivery ameliorates renal hypertrophy and fibrosis in
streptozotocin-induced diabetic rats by suppressing the Rho-associated
coiled-coil kinase signaling pathway
#MMPMID25695625
Deng M
; Luo Y
; Li Y
; Yang Q
; Deng X
; Wu P
; Ma H
Mol Med Rep
2015[Jul]; 12
(1
): 45-54
PMID25695625
show ga
The present study aimed to investigate whether klotho gene delivery attenuated
renal hypertrophy and fibrosis in streptozotocin-induced diabetic rats. A
recombinant adeno-associated virus (rAAV) carrying mouse klotho full-length cDNA
(rAAV.mKL), was constructed for in vivo investigation of klotho expression.
Diabetes was induced in rats by a single tail vein injection of 60 mg/kg
streptozotocin. Subsequently, the diabetic rats received an intravenous injection
of rAAV.mKL, rAAV.green fluorescent protein (GFP) or phosphate-buffered saline
(PBS). The Sprague-Dawley rat group received PBS and served as the control group.
After 12 weeks, all the rats were sacrificed and ELISA, immunohistochemical and
histological analyses, fluorescence microscopy, semi-quantitative reverse
transcription-polymerase chain reaction and western blottin were performed. A
single dose of rAAV.mKL was found to prevent the progression of renal hypertrophy
and fibrosis for at least 12 weeks (duration of study). Klotho expression was
suppressed in the diabetic rats, but was increased by rAAV.mKL delivery. rAAV.mKL
significantly suppressed diabetes-induced renal hypertrophy and histopathological
changes, reduced renal collagen fiber generation and decreased kidney hypertrophy
index. In addition, rAAV.mKL decreased the protein expression levels of
fibronectin and vimentin, while it downregulated the mRNA expression and activity
of Rho-associated coiled-coil kinase (ROCK)I in the kidneys of the diabetic rats.
These results indicated that klotho gene delivery ameliorated renal hypertrophy
and fibrosis in diabetic rats, possibly by suppressing the ROCK signaling
pathway. This may offer a novel approach for the long-term control and
renoprotection of diabetes.