Su Li Juan, Chang Cui Fang, Han Hong Peng, Ma Hui, Xu Cun Shuan
Ocean University of China, Qingdao 260003.
Fen Zi Xi Bao Sheng Wu Xue Bao. 2006 Jun;39(3):258-64.
Heat shock factor binding protein 1 (HSBP1), a recently discovered protein, weakens and blocks transcription of the heat shock protein 70 (HSP70) gene when binding to HSF1, but HSBP1 can promote cell growth, cell development and cell differentiation when binding to HSF2. Partial hepatectomy (PH) in rat creates injury stimulation and induces liver regeneration. How does hsbp1 coordinate two processes sequently is extremely interesting. This paper, based on cloning the full-length cDNA of hsbpl in rat, applied in situ hybridration and Rat Genome 230 2.0 Array to analyze hsbp1, hsf1, hsf2 and hsp70 expression in liver after PH and sham-operation. The results indicated that the hsbp1 expression level was down-regulated meaningfully at 0.5-2h and up-regulated meaningfully at 8-16h after sham-operation, while hsf2 expression level did not meaningfully change at 0-144h after sham-operation. hsbp1 expression level was up-regulated meaningfully at 6h and 66-144h,and hsf1 at 8-16h, hsf2 at 2-16h, hsp70 at 0.5-24h after PH. Our data suggested that up-regulated expression of the hsp70 at 0.5-12h after sham-operation was controlled by intracellular HSF1, and then controlled by hsbp1 down-regulated at 0.5-2h and hsf1 up-regulated at 8-16h. In the early phase of liver regeneration in rats, hsbp1 and hsf2 expression levels were up-regulated, which promoted cell proliferation through HSBP1 and HSF2 up-regulating,upa activating,c-jun enhancing, intracellular matrix (ECM) degradation, activating the hepatocyte-like growth factor (HGF) etc. In the late phase of liver regeneration (66-144h), hsbp1 expression level was up-regulated, which promoted reconstruction of liver structure and recovery of liver function through HSBP1 inhibiting hsp70 expression, up-regulating genes related to growth, development, differentiation. In conclusion, down-regulating of hsbp1 contributed to interaction between HSF1 and HSE,increased hsp70 expression and enhanced anti-injured capacity of liver and rats. HSBP1 and HSF2 activated the genes related to growth, development, differentiation and then promoted liver regeneration in rats.
热休克因子结合蛋白1（HSBP1）是一种最近发现的蛋白质，当它与热休克因子1（HSF1）结合时，会削弱并阻断热休克蛋白70（HSP70）基因的转录，但当它与热休克因子2（HSF2）结合时，HSBP1可以促进细胞生长、细胞发育和细胞分化。大鼠部分肝切除术（PH）会造成损伤刺激并诱导肝再生。HSBP1如何依次协调这两个过程非常有趣。本文基于克隆大鼠HSBP1的全长cDNA，应用原位杂交和大鼠基因组230 2.0芯片分析PH和假手术后肝脏中HSBP1、HSF1、HSF2和HSP70的表达。结果表明，假手术后0.5 - 2小时HSBP1表达水平显著下调，8 - 16小时显著上调，而假手术后0 - 144小时HSF2表达水平无显著变化。PH后6小时、66 - 144小时HSBP1表达水平显著上调，8 - 16小时HSF1上调，2 - 16小时HSF2上调，0.5 - 24小时HSP70上调。我们的数据表明，假手术后0.5 - 12小时HSP70表达上调由细胞内HSF1控制，随后由0.5 - 2小时下调的HSBP1和8 - 16小时上调的HSF1控制。在大鼠肝再生早期，HSBP1和HSF2表达水平上调，通过HSBP1和HSF2上调、激活、增强c-jun、降解细胞外基质（ECM）、激活肝细胞生长因子（HGF）等促进细胞增殖。在肝再生后期（66 - 144小时），HSBP1表达水平上调，通过抑制HSP70表达、上调与生长、发育、分化相关的基因促进肝脏结构重建和肝功能恢复。总之，HSBP1下调有助于HSF1与热休克元件（HSE）相互作用，增加HSP70表达，增强肝脏和大鼠的抗损伤能力。HSBP1和HSF2激活与生长、发育、分化相关的基因，进而促进大鼠肝再生。
