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[摘要]：Background. Renal ischemia-reperfusion injury (IRI) largely contributes to kidney transplant dysfunction and acute kidney injury, but its pathogenesis is not fully understood. In this study, the role of transforming growth factor (TGF)-beta 1 in renal IRI is investigated using TGF-beta 1 deficient mice.Method. Human renal tubular epithelial cells (TEC) line (HK-2) was used as an in vitro model, and cell apoptosis was determined by flow cytometric analysis. Renal IRI was induced in mice by clamping renal vein and artery for 45 min at 32 degrees C.Results. Here, we showed that in cultures of HK-2 cells, TGF-beta 1 expression was up-regulated by tumor necrosis factor (TNF)-alpha. Neutralization of TGF-beta 1 activity increased both spontaneous and TNF-alpha-mediated apoptosis, and knockdown of TGF-beta 1 expression increased the sensitivity of cell apoptosis to TNF-alpha. In a mouse model of renal IRI, a deficiency in TGF-beta expression increased the severity of renal injury, as indicated by more severe renal tubular damage, higher levels of serum creatinine or blood urea nitrogen in TGF-beta 1 deficient mice as compared with those in wild-type controls. Further experiments showed that the antiapoptosis of TGF-beta 1 correlated with up-regulation of Bcl-2 in kidney cells.Conclusion. Expression of TGF-beta 1 in TECs, potentially induced by proinflammatory TNF-alpha, renders TECs resistance to cell death. In mice, TGF-beta 1 deficiency results in more prone to IRI. These data imply that TGF-beta 1 may act as a feedback survival factor in the resistance to kidney injury and maintenance of epithelium homeostasis. |
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