title: Transforming growth factor-beta1 and Smad4 signaling pathway down-regulates renal extracellular matrix degradation in diabetic rats.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathophysiology, Guiyang Medical College, Guiyang. qinyang@gmc.edu.cn
authors.forename: Qin
authors.initials: Q
authors.lastname: Yang
authors.forename: Ru-jia
authors.initials: RJ
authors.lastname: Xie
authors.forename: Ting
authors.initials: T
authors.lastname: Yang
authors.forename: Li
authors.initials: L
authors.lastname: Fang
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.forename: Guo-zhong
authors.initials: GZ
authors.lastname: Zhang
authors.forename: Ming-liang
authors.initials: ML
authors.lastname: Cheng
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D015536:Down-Regulation; D005109:Extracellular Matrix / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D051901:Smad4 Protein / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D051901:Smad4 Protein; D053773:Transforming Growth Factor beta1