Effect of bone marrow-derived mesenchymal stem cells on TGF-β1/Smad signaling pathway during acute lung injury in rats

Abstract

Objective To evaluate the effect of bone marrow-derived mesenchymal stem cells(BMSCs)on transforming growth factor-β1(TGF-β1)/Smad signaling pathway during acute lung injury(ALI)in rats. Methods Healthy clean-grade adult male Sprague-Dawley rats, aged 4-5 weeks, weighing 100-120 g, were selected, and BMSCs were prepared and cultured in vitro.Eighty-four healthy clean-grade adult male Sprague-Dawley rats, aged 4 weeks, weighing 170-190 g, were selected and divided into 4 groups(n=21 each)using a random number table method: control group(group C), group ALI, ALI plus BMSCs group(group ALI+ BMSCs), and ALI plus phosphate buffer solution(PBS)group(group ALI+ PBS). ALI was induced by intraperitoneally injecting 5 mg/kg lipopolysaccharide 0.5 ml in anesthetized rats.In group ALI+ BMSCs, 1×104 cells/ml BMSCs 0.5 ml(in PBS)was injected via the tail vein after intraperitoneal injection of lipopolysaccharide.PBS 0.5 ml was injected via the tail vein after intraperitoneal injection of lipopolysaccharide in group ALI+ PBS.Arterial blood samples were collected at 6, 24 and 48 h after injecting BMSCs for blood gas analysis and for determination of wet to dry weight ratio(W/D ratio), pathological changes(using haematoxylin and eosin staining), and expression of TGF-β1, Smad2 and Smad3 in lung tissues(by Western blot). Results Compared with group C, PaO2 was significantly decreased, PaCO2 and W/D ratio were increased, the expression of TGF-β1, Smad2 and Smad3 in lung tissues was up-regulated(P<0.05), and the pathological changes of lung tissues were accentuated in ALI, ALI+ BMSCs and ALI+ PBS groups.Compared with group ALI, PaO2 was significantly increased, PaCO2 and W/D ratio were decreased, the expression of TGF-β1, Smad2 and Smad3 in lung tissues was down-regulated(P<0.05), and the pathological changes of lung tissues were significantly reduced in group ALI+ BMSCs. Conclusion The mechanism by which BMSCs mitigates ALI may be associated with inhibiting TGF-β1/Smad signaling pathway in rats. Key words: Mesenchymal stem cell transplantation; Transforming growth factor beta 1; Smad Proteins; Respiratory distress syndrome, adult