Background: During the development of obliterative bronchiolitis (OB), extensive extracellular matrix is deposited in the lumen of the bronchioli, and the number of myofibroblasts increases. Some researchers have demonstrated that apoptosis of epithelium cells is correlated with OB, but the mechanism is not clear. By triggering/suppressing the apoptosis of tracheal epithelial cell (TECs) by transfecting p53 or Bcl-xl gene in vitro, we want to make a primary study on the effect of apoptosis of TECs, then we could investigate the influence and mechanism of TECs on the biological behavior of BMSCs and elucidate the pathogenesis of OB.

Methods and Results: TECs of mice were isolated and cultured in vitro, p53 and Bcl-xl genes lentivirus vector were constructed and applied to transfect TECs. We found p53 over-expression TECs showed higher apoptosis rate and Bcl-xl over-expression TECs showed lower apoptosis rate (P<0.05). BMSCs from mice were co-cultured with the transfected TECs in the Transwell chamber for 72h. The proliferation rate of BMSCs after being co-cultured in the p53 group has increased, while the proliferation rate in the Bcl-xl group has declined. Through methods of immunocytochemistry and flow cytometry, we find that the expression of α-SMA and vimentin in BMSCs have significantly strengthened in p53 group; the expression in the Bcl-xl group is similar to that of normal group. These means the apoptosis of TECs would stimulate the differentiation of BMSCs to myofibroblasts. Use the ELISA method to test the cytokines in p53 gene transfected TECs supernatant, it showed increased expression of TGF-β and SDF-1. When this supernatant was added in BMSCs media, the ability of proliferation, migration and differentiation of BMSCs increased. When repeating experiments with SDF-1 or TGF-β antibody added in culture media separately, the results confirmed that SDF-1 promoted the migration of BMSCs, while TGF-β induced the proliferation and differentiationof BMSCs.

Conclusion: This study indicated that the apoptotic TECs in OB might increase the amount of myofibroblasts derived from recipient's BMSCs. Therapeutic methods aimed at preventing apoptosis of TECs may improve the outcome of lung transplantation.

CITATION INFORMATION: Zhang X, Xia T, Wang C, Jiang K, Wang J, Nie J. The Impact of Tracheal Epithelial Cells Apoptosis on the Biological Behavior of Bone Marrow Mesenchymal Stem Cells (BMSCs) in OB. Am J Transplant. 2017;17 (suppl 3).

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