RESUMEN
Objective To investigate the role of overexpression of Smad7,the inhibitory factor of TGF-?/Smads signaling,in epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells.Methods Peritoneal fibrosis rat model was built by daily intraperitoneal injection with 4.25% Dineal (100 ml/kg) and lipopolysaccharide(LPS) (0.6 mg/kg) at day 8,10,12,22,24,26. Smad7 or control empty vectors was transferred at day 0,14 and was induced by doxycline in the daily drinking water (200 mg/L).Rats were sacrificed on day 28 and the expression of TGF-beta/ Smads,?-SMA and E-cadherin was examined.Results Compared with normal rats,empty vector rats showed higher expression of phosphorylated Smad2/3.?-SMA expression was elevated but E-cadherin was reduced.Under electron microscope,the mesothelial cells removed to submesothelial zone and showed large bundles of actin microfilaments and dense bodies within the cytoplasm. Basement membrane was broken.After induction of Smad7 in peritoneal fibrosis rats,the morphology of mesothelial ceils normalized partly,phosphorylated Smad2/3 was reduced.Moreover,expression of E-cadherin was increased,expression of?-SMA was dramatically reduced.Conclusion Inhibition of TGF-?/Smad signaling by Smad7 overexpression may inhibit the epithelial-mesenchymal transition of mesothelial cell,which may provide a new therapeutic method for peritoneal fibrosis by overexpression of Smad7.