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HSF4B通过上调RhoA和Rac1促进晶状体上皮细胞迁移 被引量：4

HSF4B Increases Migration of Lens Epithelial Cell by Up-regulating the Expression of RhoA and Rac1
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摘要 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 regulator of postnatal lens development by involving the regulation of lens epithelial cell proliferation and fibroblast differentiation. We found that the expression of Hsp25 and aB-crystallin was up-regulated in HSF4b-reconstituted mLEC/HA-HSF4b cells. The results of wound-healing and Transwel! assays indicated that the migration of mLEC/HA-HSFdb cells was significantly faster than that of mLEC/HSF4-/-cells （ P = 0. 0001 ）. The immunoblotting and semi- quantity RT-PCR data showed that HSF4b up-regulated the expression of RhoA, Racl and CDC42 and correlated with the Hsp25 and ctB-crystallin levels, except for CDC42. We hypothesized that HSF4b might regulate the migration of anterior epithelial cell to posterior by increasing the expression of RhoA and Racl.
作者 张军 马增翼 李淑莲 刘广超 胡延忠
机构地区 河南大学医学院细胞与分子免疫学重点实验室 复旦大学附属华山医院神经外科
出处 《中国生物化学与分子生物学报》 CAS CSCD 北大核心 2013年第4期377-382,共6页 Chinese Journal of Biochemistry and Molecular Biology
基金 国家自然科学基金资助(No.30871299 No.81270985)~~
关键词 热休克转录因子4 晶状体上皮细胞 RHOA RAC1 热休克蛋白25 αB-晶体蛋白 heat shock factor 4 （ HSF4 ） mouse lens epithelial cell RhoA Racl heat shock protein25 （Hsp25） ctB-crystallin
分类号 Q78 [生物学—分子生物学]
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参考文献15

  • 1Bu L, Jin Y, Shi Y, et al. Mutant DNA-binding domain of HSF4 is associated with autosomal dominant lamellar and Marner cataract[J]. Nat Genet, 2002, 31(3) : 276-278.
  • 2Min J N, Zhang Y, Moskophidis D, et al. Unique contribution of heat shock transcription factor 4 in ocular lens development and fiber cell differentiation [ J ]. Genesis, 2004, 40 (4) :205-217.
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同被引文献44

  • 1吴明星,吴开力,卞庆宁,姬红培,王忠浩,刘奕志.年龄相关性白内障晶体上皮细胞的基因表达谱变化的初步分析[J].中国病理生理杂志,2006,22(7):1429-1434. 被引量：4
  • 2Min JN, Zhang Y, Moskophidis D, et al. Unique contri- bution of heat shock transcription factor 4 in ocular lens development and fiber cell differentiation [ J ]. Genesis, 2004, 40(4) :205-217.
  • 3Merath K, Ronchetti A, Sidjanin DJ. Functional analysis of HSF4 mutations found in patients with autosomal reces- sive congenital cataracts [ J ]. Invest Ophthalmol Visual Sei, 2013, 54(10):6646-6654.
  • 4Zhang J, Ma Z, Wang J, et al. Regulation of Hsf4b nu- clear translocation and transcription activity by phosphoryl- ation at threonine 472[ J]. Bioehim Biophys Aeta, 2014, 1843(3) :580-589.
  • 5Hu Y, Zhang J, Wang C, et al. The transcription activity of heat shock factor 4b is regulated by FGF2 [ J ]. Int J Biochem Cell Biol, 2013, 45(2) :317-325.
  • 6Nakai A, Tanabe M, Kawazoe Y, et al. HSF4, a new member of the human heat shock factor family which lacks properties of a transcriptional activator[ J]. Mol Cell Biol, 1997, 17(1) :469-481.
  • 7Ke T, Wang QK, Ji B, et al. Novel HSF4 mutation cau- ses congenital total white cataract in a Chinese family[ J]. Am J Ophthalmol, 2006, 142(2) :298-303.
  • 8Bu L, Jin Y, Shi Y, et al. Mutant DNA-binding domain of HSF4 is associated with autosomal dominant lamellar and Marner cataract[J]. Nat Genet, 2002, 31 (3) :276- 278.
  • 9Cui X, Zhang J, Du R, et al. HSF4 is involved in DNA damage repair through regulation of Rad51 [ J ]. Biochim Biophys Acta, 2012, 8(15) : 1308-1315.
  • 10Enoki Y, Mukoda Y, Furutani C, et al. DNA-binding and transcriptional activities of human HSF4 containing muta- tions that associate with congenital and age-related cata- racts[ J ]. Biochim Biophys Acta, 2010, 1802 (9) :749- 753.

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中国生物化学与分子生物学报
2013年 第4期

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