Effects of Silencing Transforming Growth Factor-β1 by RNA Interference Plasmid on Rat Renal Allograft Fibrosis Using Smads Pathway - 20/08/11
Résumé |
Objectives |
To evaluate the effects of transforming growth factor (TGF)-β1 RNA interference plasmid on rat renal allograft fibrosis and to explore its mechanisms.
Methods |
A Sprague-Dawley to Wistar rat transplant kidney-sclerosis accelerated model was constructed and transfected with short hairpin RNA-TGF-β1 based on the hydromechanics. Kidney and blood samples were collected at the first, second, and third months after transplantation. Reverse transcriptase-polymerase chain reaction and Western blotting were used to detect the expression of TGF-β1, phosphorylated Smad3/7, E-cadherin, and type I collagen. The fibrosis extent was assessed using Masson staining. The immunohistochemical staining of E-cadherin and ⍺-smooth muscle actin were used to label the tubular epithelial cells and fibroblast, respectively.
Results |
The blood urea nitrogen and serum creatinine were lower in the plasmid group than in the control groups (P <.05 and P <.01, respectively). The expression of TGF-β1 was significantly inhibited by the plasmid and its target gene type I collagen (P <.05 or P <.01), in which the signal proteins of phosphorylated Smad3 was downregulated and phosphorylated Smad7 was upregulated. Also, the fibrosis of the renal allograft was improved and milder fibrosis was present in the plasmid group. In addition, short hairpin RNA-TGF-β1 plasmid maintained the expression of E-cadherin on tubular epithelial cells, resulting in inhibition of cell transdifferentiation from epithelial cells to fibroblast.
Conclusions |
Our results suggest that short hairpin RNA-TGF-β1 plasmid could prevent the fibrosis of renal allografts. The mechanism might be associated with its effects of downregulating phosphorylated Smad3 and upregulating phosphorylated Smad7, leading to the suppression of epithelial-myofibroblast transdifferentiation and extracellular matrix synthesis.
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Yuguo Xia and Zhikang Yin contributed equally to this work. |
Vol 77 - N° 3
P. 762.e1-762.e7 - mars 2011 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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