| OBJECTIVESTendon adhesion which seriously affect the limb function is a difficult task for clinical hand surgery.The mechanism of tendon adhesion is still unclear.It is known that the transcription factor NF-?B RelA/p65 plays a key role in fibrotic diseases such as liver and kidney fibrosis.The aim of this study was to explore the effect and associated mechanism of p65 in tendon adhesion and provide a new theoretical basis for adhesion treatment.METHODSThe gene expression,expression of p65 and extracellular matrix in human tendon fibrotic tissues were detected.In addition,the correlation between p65 and tendon adhesion was investigated in the rat tendon injury model.After p65 inhibition in vivo by small interfering(si)RNA,the effects of p65 on tendon adhesion was evaluated.Further,after the inhibition of p65 by siRNA or p65 specific inhibitor(Helenalin or JSH23)in vitro in fibroblasts,the effect and mechanism of p65 on tendon adhesion formation was evaluated.RESULTSAs shown by the gene chip assay,the expression of NF-?B pathway in tendon fibrotic tissues was up-regulated compared with normal human tissues.Immunohistochemistry and Western blot showed that p65 and extracellular matrix proteins were up-regulated in human fibrotic tissues.Secondly,the expression of p65 was positively correlated with the levels of tendon adhesion,extracellular matrix and inflammatory factor expression in rats.Moreover,after in vivo p65 inhibition,the level of adhesion,expression of extracellular matrix and inflammatory factor were decreased.Lastly,the in vitro study in which p65 was inhibited showed the decrease of cell proliferation,increase of cell apoptosis,and down-regulation of extracellular matrix and inflammatory factor expression.CONCLUSIONSRelA/p65 plays a crucial role in the formation of tendon adhesion.P65 inhibition prevents adhesion formation by suppressing inflammation,inhibiting proliferation and promoting apoptosis of fibroblasts,which provide a new angle for tendon adhesion treatment. |
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