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【Cell】活化星型细胞的衰老可抑制肝脏纤维化
Senescence of Activated Stellate Cells Limits Liver Fibrosis
Valery Krizhanovsky,1 Monica Yon,1,3 Ross A. Dickins,1 Stephen Hearn,1 Janelle Simon,1,2 Cornelius Miething,1 Herman Yee,4 Lars Zender,1,5 and Scott W. Lowe1,2,*
Cellular senescence acts as a potent mechanism of tumor suppression; however, its functional contribution to noncancer pathologies has not been examined. Here we show that senescent cells accumulate in murine livers treated to produce fibrosis, a precursor pathology to cirrhosis. The senescent cells are derived primarily from activated hepatic stellate cells, which initially proliferate in response to liver damage and produce the extracellular matrix deposited in the fibrotic scar. In mice lacking key senescence regulators, stellate cells continue to proliferate, leading to excessive liver fibrosis. Furthermore, senescent activated stellate cells exhibit gene expression profile consistent with cell-cycle exit, reduced secretion of extracellular matrix components, enhanced secretion of extracellular matrix-degrading enzymes, and enhanced immune surveillance. Accordingly natural killer cells preferentially kill senescent activated stellate cells in vitro and in vivo, thereby facilitating the resolution of fibrosis. Therefore, the senescence program limits the fibrogenic response to acute tissue damage. 本人已令人另本文翻译48小时未提交请其他战友继续认领 Senescence of Activated Stellate Cells Limits Liver Fibrosis
Valery Krizhanovsky,1 Monica Yon,1,3 Ross A. Dickins,1 Stephen Hearn,1 Janelle Simon,1,2 Cornelius Miething,1 Herman Yee,4 Lars Zender,1,5 and Scott W. Lowe1,2,*
Cellular senescence acts as a potent mechanism of tumor suppression; however, its functional contribution to noncancer pathologies has not been examined.
细胞衰老作为抑制肿瘤的一种有效的机制，但其引起非癌性病理改变的支配效能还未曾被检测。
Here we show that senescent cells accumulate in murine livers treated to produce fibrosis, a precursor pathology to cirrhosis.
在这里我们展示在鼠类的肝脏中堆积衰老细胞用于使肝脏纤维化，肝脏纤维化是肝硬化的前驱病理改变。
The senescent cells are derived primarily from activated hepatic stellate cells, which initially proliferate in response to liver damage and produce the extracellular matrix deposited in the fibrotic scar.
这些衰老细胞主要由活化的肝星形细胞衍生而来。肝星形细胞的增生最初是机体对肝脏损伤的反应并产生沉积在纤维疤痕中的细胞外基质。
In mice lacking key senescence regulators, stellate cells continue to proliferate, leading to excessive liver fibrosis.
缺乏关键衰老调节因子的老鼠，星形细胞持续增生将导致肝脏过度纤维化。
Furthermore, senescent activated stellate cells exhibit gene expression profile consistent with cell-cycle exit, reduced secretion of extracellular matrix components, enhanced secretion of extracellular matrix-degrading enzymes, and enhanced immune surveillance.
此外衰老的活化星形细胞描绘的基因表达谱与细胞周期的引出端一致，它使细胞外基质的分泌减少，细胞外基质降解酶分泌增加并且还增强了老鼠的免疫监视力。
Accordingly natural killer cells preferentially kill senescent activated stellate cells in vitro and in vivo, thereby facilitating the resolution of fibrosis. Therefore, the senescence program limits the fibrogenic response to acute tissue damage.
在小鼠体内及体外，自然杀伤细胞相应地优先消灭衰老的活化星形细胞，并藉此促进纤维化的消解。因此衰老程序限制了急性组织损伤中的纤维化反应。 细胞衰老作为抑制肿瘤的一种有效的机制，但其引起非癌性病理改变的支配效能还未曾被检测。在这里我们展示在鼠类的肝脏中堆积衰老细胞用于使肝脏纤维化，肝脏纤维化是肝硬化的前驱病理改变。这些衰老细胞主要由活化的肝星形细胞衍生而来。肝星形细胞的增生最初是机体对肝脏损伤的反应并产生沉积在纤维疤痕中的细胞外基质。缺乏关键衰老调节因子的老鼠，星形细胞持续增生将导致肝脏过度纤维化。此外衰老的活化星形细胞描绘的基因表达谱与细胞周期的引出端一致，它使细胞外基质的分泌减少，细胞外基质降解酶分泌增加并且还增强了老鼠的免疫监视力。在小鼠体内及体外，自然杀伤细胞相应地优先消灭衰老的活化星形细胞，并藉此促进纤维化的消解。因此衰老程序限制了急性组织损伤中的纤维化反应。 [标签:content1][标签:content2]
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作者:admin@医学,生命科学 2011-10-28 05:46
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