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MiRNA-29c regulates the expression of inflammatory cytokines in diabetic
nephropathy by targeting tristetraprolin
#MMPMID28539664
Guo J
; Li J
; Zhao J
; Yang S
; Wang L
; Cheng G
; Liu D
; Xiao J
; Liu Z
; Zhao Z
Sci Rep
2017[May]; 7
(1
): 2314
PMID28539664
show ga
Diabetic nephropathy is one of the most prevalent chronic complications of
Diabetes mellitus, but its pathogenesis remains elusive. This study was designed
to determine the role of tristetraprolin (TTP), inflammatory cytokines and
microRNAs (miRNAs) in DN. The blood and urine samples were obtained from 32
patients with DN, 33 patients with type 2 DM, and 35 normal healthy subjects as
controls. Renal tissue samples were also obtained from 10 DN patients and 10
normal controls. The miRNA microarray analyses were performed in pooled plasma
and urine sediment samples of eight DN patients and eight age- and sex-matched
health control subjects and three paired renal tissues from patients with DN and
normal controls. Conditionally immortalized mouse podocytes (MPC5) were used a
cell model. The expressions of TTP and cytokines in patient samples and cultured
cells were determined by qRT-PCR and Western blotting or ELISA. Our results
indicated that miRNA-29c directly targeted TTP and promoted inflammatory response
under hyperglycemic conditions. Overexpression of miRNA-29c in podocytes resulted
in an increase in inflammatory cytokines and inhibition of miRNA-29c by using its
inhibitor reduced the inflammatory cytokines in podocytes. Finally, miRNA-29c
promoted the progression of DN by targeting TTP, providing a target for a
therapeutic intervention of DN.