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热休克转录因子4(heat shock transcription factor 4,HSF4)是调控新生儿期晶状体发育的关键转录因子.它参与调控晶状体上皮细胞增生和纤维细胞分化,然而其作用机理仍不清楚.利用鼠晶状体上皮细胞mLEC/HSF4-/-和mLEC/HA-HSF4b细胞为材料,对HSF4在晶状体上皮细胞中的调控作用进行研究.结果发现,重建的mLEC/HA-HSF4b细胞中,高表达热休克蛋白25(Hsp25)和αB晶体蛋白(αB-crystallin).细胞划痕实验和Transwell细胞迁移实验结果表明,mLEC/HSF4-/-细胞明显比mLEC/HA-HSF4b细胞的迁徙速度慢(t检验,P=0.0001).应用免疫印迹和半定量RT-PCR实验发现,HSF4b能上调RhoA,Rac1和CDC42的表达.但后者的表达不受Hsp25和αB-crystallin调控.由此推论,HSF4b通过调控RhoA,Rac1和CDC42的表达参与调控晶状体上皮细胞向后房的迁徙.这一新发现对解释HSF4b调控晶状体发育提供了有力的证据.
Heat shock transcription factor 4 (HSF4) is a key transcription factor that regulates the development of lens in neonatal period, and it is involved in the regulation of lens epithelial cell proliferation and fibroblast differentiation. However, its mechanism of action remains unclear. The effects of HSF4 on lens epithelial cells were investigated in mLEC / HSF4 - / - and mLEC / HA-HSF4b cells.The results showed that the highly expressed heat shock protein 25 Hsp25 and αB-crystallin. The results of cell scratch assay and Transwell cell migration showed that mLEC / HSF4 - / - cells were significantly slower than that of mLEC / HA-HSF4b cells (t test, P = 0.0001 ). Western blotting and semi-quantitative RT-PCR experiments showed that HSF4b upregulated the expression of RhoA, Rac1 and CDC42, but the latter was not regulated by Hsp25 and αB-crystallin, suggesting that HSF4b could regulate RhoA, Rac1 and The expression of CDC42 is involved in the regulation of the migration of lens epithelial cells into the posterior chamber.The new findings provide strong evidence to explain the regulation of lens development by HSF4b.