Transforming growth factor-beta1 and Smad4 signaling pathway down-regulates renal extracellular matrix degradation in diabetic rats / 中国医学科学杂志(英文版)
Chinese Medical Sciences Journal
; (4): 243-249, 2007.
Article
em En
| WPRIM
| ID: wpr-243520
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WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the role of transforming growth factor-beta1 (TGF-beta1)/Smad4 pathway in development of renal fibrosis in streptozotocin (STZ)-induced diabetic nephropathy (DN) rats and explore its possible mechanism.</p><p><b>METHODS</b>Male Wistar rats weighing 180-220 g were divided into 5 groups: group A (normal control), group B [diabetes mellitus (DM) 2 weeks], group C (DM 4 weeks), group D (DM 8 weeks), and group E (DM 16 weeks). Except for the normal control group, other groups were induced DM by single injection of STZ (55 mg/kg) respectively. Blood glucose level, serum creatinine, and 24-hour urine protein were examined. Expressions of TGF-beta1 and Smad4 protein and mRNA in kidney were detected using immunohistochemical technique, Western blot, and real-time PCR. mRNA expressions of stromelysin-1 (MMP-3), tissue inhibitor of metalloproteinase-1 (TIMP-1), and collagen In in kidney were also detected by real-time PCR.</p><p><b>RESULTS</b>The levels of blood glucose, serum creatinine, and 24-hour urine protein in rats of group B, C, D, and E were higher than those of the control group. With the progression of renal fibrosis, the expressions of TGF-beta1 and Smad4 protein and mRNA in kidney of diabetic rats elevated. In addition, the renal MMP-3 mRNA expression diminished in diabetic rats, while TIMP-1 and collagen III mRNA increased.</p><p><b>CONCLUSIONS</b>In STZ-induced diabetic rats, the TGF-beta1/Smad4 appears to play an important role in renal fibrosis of DN. The increased expression of TGF-beta1 and Smad4 might result in the transcriptional regulation of downstream target genes of TGF-beta1/Smad4 pathway, which contributes to the progression of renal fibrosis in diabetic rats.</p>
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Assunto principal:
Sequência de Bases
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Transdução de Sinais
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Regulação para Baixo
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Ratos Wistar
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Primers do DNA
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Diabetes Mellitus Experimental
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Proteína Smad4
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Matriz Extracelular
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Fator de Crescimento Transformador beta1
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Genética
Limite:
Animals
Idioma:
En
Revista:
Chinese Medical Sciences Journal
Ano de publicação:
2007
Tipo de documento:
Article