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首页> 外文期刊>Journal of Cellular Physiology >Shear stress upregulates regeneration‐related immediate early genes in liver progenitors in 3D ECM‐like microenvironments
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Shear stress upregulates regeneration‐related immediate early genes in liver progenitors in 3D ECM‐like microenvironments

机译：剪切应力移植再生有关立即早期基因在肝脏祖细胞在3 d

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摘要

The role of fluid stresses in activating the hepatic stem/progenitor cell regenerative response is not well understood. This study hypothesized that immediate early genes (IEGs) with known links to liver regeneration will be upregulated in liver progenitor cells (LPCs) exposed to in vitro shear stresses on the order of those produced from elevated interstitial flow after partial hepatectomy. The objectives were: (1) to develop a shear flow chamber for application of fluid stress to LPCs in 3D culture; and (2) to determine the effects of fluid stress on IEG expression in LPCs. Two hours of shear stress exposure at ～4?dyn/cm 2 was applied to LPCs embedded individually or as 3D spheroids within a hyaluronic acid/collagen I hydrogel. Results were compared against static controls. Quantitative reverse transcriptase polymerase chain reaction was used to evaluate the effect of experimental treatments on gene expression. Twenty‐nine genes were analyzed, including IEGs and other genes linked to liver regeneration. Four IEGs (CFOS, IP10, MKP1, ALB) and three other regeneration‐related genes (WNT, VEGF, EpCAM) were significantly upregulated in LPCs in response to fluid mechanical stress. LPCs maintained an early to intermediate stage of differentiation in spheroid culture in the absence of the hydrogel, and addition of the gel initiated cholangiocyte differentiation programs which were abrogated by the onset of flow. Collectively the flow‐upregulated genes fit the pattern of an LPC‐mediated proliferative/regenerative response. These results suggest that fluid stresses are potentially important regulators of the LPC‐mediated regeneration response in liver.
机译：流体压力在激活的作用肝干细胞/祖细胞再生反应不是很好理解。假设立即早期基因(ieg)已知与肝再生调节肝脏祖细胞(lpc)暴露在体外剪切应力的秩序从高架间隙流的产生后部分肝切除术。(1)开发的剪切流室应用3 d lpc的流体压力文化;流体压力IEG lpc的表达式。剪切应力接触~ 4 ?lpc的嵌入式应用单独或作为3 d在一个透明质酸/胶原蛋白我球状体水凝胶。控制。聚合酶链反应被用来评估实验在基因治疗的效果表达式。包括ieg和其他基因与肝有关再生.和其他三个再生相关基因(WNTVEGF, EpCAM)显著调节lpc的流体机械应力。保持一个早期的中间阶段在球体文化分化缺乏水凝胶,凝胶发起cholangiocyte分化程序开始废除的流。适应集体流量调节基因一个LPC的介导的模式增殖/再生反应。结果表明,流体的压力潜在的重要的监管机构LPC的介导肝再生反应。

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