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Mycophenolate mofetil ameliorates diabetic nephropathy through epithelial
mesenchymal transition in rats
#MMPMID26080907
Xiao X
; Wang J
; Chang X
; Zhen J
; Zhou G
; Hu Z
Mol Med Rep
2015[Sep]; 12
(3
): 4043-4050
PMID26080907
show ga
Recent studies in animal models have revealed that mycophenolate mofetil (MMF)
has certain protective effects against experimental diabetic nephropathy. The
present study therefore aimed to investigate the hypothesis that diabetic
nephropathy may be ameliorated by mycophenolate mofetil and benazepril treatment
alone or in combination, and identify the potential underlying mechanisms in a
rat model. Diabetes was induced in rats by a single intraperitoneal injection of
streptozotocin. Rats were subsequently treated with benazepril, MMF or a
combination of the two drugs, and blood glucose, normalized kidney weight, urine
protein and serum creatinine were determined. The pathological changes in renal
tissue were also observed. In addition, indices of epithelial mesenchymal
transition, including ??smooth muscle actin (??SMA) and transforming growth
factor (TGF)??1 expression, were examined. Normalized kidney weight, urine
protein and serum creatinine levels were significantly improved in the diabetic
rats treated with benazepril or mycophenolate mofetil, compared with those of
rats in the untreated diabetic group. Pathological changes in the kidney were
detected concurrently with increasing kidney weight and urinary albumin
excretion, with a similar trend in variation among groups. In addition, the
expression of epithelial mesenchymal transition indices, including ??SMA and
TGF??1, in the renal tubule interstitium were significantly decreased in the
benazepril? and MMF?treated groups compared with those of the diabetic group. As
expected, the aforementioned indices were markedly lower in the benazepril and
MMF combined treatment group than those in the single medication groups. These
data suggested that MMF may have a protective role in diabetic nephropathy, and
that the underlying mechanism may be partially dependent upon the suppression of
the epithelial mesenchymal transition. Furthermore, the combination of benazepril
and MMF conferred enhanced efficacy over monotherapies in the treatment of
diabetic nephropathy.
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