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
in English
| WPRIM
| ID: wpr-243520
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>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Base Sequence
/
Signal Transduction
/
Down-Regulation
/
Rats, Wistar
/
DNA Primers
/
Diabetes Mellitus, Experimental
/
Smad4 Protein
/
Extracellular Matrix
/
Transforming Growth Factor beta1
/
Genetics
Limits:
Animals
Language:
English
Journal:
Chinese Medical Sciences Journal
Year:
2007
Type:
Article
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