HIF-1: an age-dependent regulator of lens cell proliferation.
HIF-1: an age-dependent regulator of lens cell proliferation.
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HIF-1：晶状体细胞增殖的年龄依赖性调节剂。
DOI：
10.1167/iovs.08-2118
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发表时间：
2008
影响因子：
4.4
通讯作者：
Beebe,DavidC
中科院分区：
文献类型：
--
作者：
Shui,Ying-Bo;Arbeit,JeffreyM;Johnson,RandallS;Beebe,DavidC
目的.透镜在整个生命过程中生长，并且透镜大小是核性和皮质性白内障的主要危险因素。先前的一项研究表明，透镜周围的缺氧环境抑制了老年大鼠的透镜生长。本研究旨在探讨透镜细胞增殖的年龄依赖性下降的机制。将在透镜中表达Cre重组酶的转基因小鼠与含有floxed Hif 1a等位基因的小鼠交配。将在透镜上皮细胞中表达氧不敏感型HIF-1α的转基因小鼠暴露于室内空气或60%氧气中。用BrdU标记法检测细胞增殖，用TUNEL法检测细胞死亡。在组织切片中评估形态学。Western blot检测HIF-1α和p27 KIP 1的表达。HIF调控基因的表达进行了评估微阵列。缺乏Hif 1a的晶状体退化，排除了在老年动物中的研究。呼吸60%的氧气降低了年轻和老年晶状体的透镜上皮细胞中HIF-1α水平和HIF-1调节的转录本。氧不敏感HIF-1α的过表达对透镜大小没有影响，但抑制了对氧反应的增殖。全身注射铁螯合剂1，10-菲咯啉可阻止HIF-1α的降解并减少氧诱导的增殖。增加氧气降低了老年小鼠上皮细胞中p27 KIP 1的水平，这是通过表达氧不敏感形式的HIF-1α来防止的。HIF-1α存在，并且HIF-1在整个生命过程中都是转录活性的，但仅在较旧的晶状体中抑制生长。在旧镜片中维持p27 KIP 1水平升高需要HIF-1。p27 KIP 1和其它生长调节剂可以选择性地抑制较老的透镜上皮细胞的增殖。
purpose. The lens grows throughout life, and lens size is a major risk factor for nuclear and cortical cataracts. A previous study showed that the hypoxic environment around the lens suppressed lens growth in older rats. The present study was conducted to investigate the mechanism responsible for the age-dependent decline in lens cell proliferation.methods. Transgenic mice expressing Cre recombinase in the lens were bred to mice containing floxed Hif1a alleles. Transgenic mice expressing oxygen insensitive forms of HIF-1α in lens epithelial cells were exposed to room air or 60% oxygen. Proliferation was measured by BrdU labeling and cell death by using the TUNEL assay. Morphology was assessed in histologic sections. HIF-1α and p27 KIP1 levels were determined by Western blot. The expression of HIF-regulated genes was assessed on microarrays.results. Lenses lacking Hif1a degenerated, precluding study in older animals. Breathing 60% oxygen reduced HIF-1α levels and HIF-1-regulated transcripts in lens epithelial cells from young and older lenses. Overexpression of oxygen-insensitive HIF-1α had no effect on lens size, but suppressed increased proliferation in response to oxygen. Systemic injection of the iron chelator, 1, 10-phenanthroline prevented the degradation of HIF-1α and reduced oxygen-induced proliferation. Increasing oxygen decreased levels of p27 KIP1 in the epithelial cells of older mice, which was prevented by expressing oxygen-insensitive forms of HIF-1α.conclusions. HIF-1α is present and HIF-1 is transcriptionally active throughout life, but suppresses growth only in older lenses. Maintaining elevated levels of p27 KIP1 in older lenses requires HIF-1. p27 KIP1 and other growth regulators may selectively suppress the proliferation of older lens epithelial cells.
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影响因子：
10.5
作者：
E. Schipani;H. Ryan;Susanna Didrickson;Tatsuya Kobayashi;M. Knight;R. Johnson
通讯作者：
E. Schipani;H. Ryan;Susanna Didrickson;Tatsuya Kobayashi;M. Knight;R. Johnson
影响因子：
4.4
作者：
T. Wong;P. Foster;G. Johnson;S. Seah
通讯作者：
T. Wong;P. Foster;G. Johnson;S. Seah
缺氧诱导的二酰甘油在调节HIF-1α活性中的作用
影响因子：
3.1
作者：
Elisa Temes;Silvia Martin;Julián Aragonés;David R. Jones;G. Olmos;I. Mérida;M. Landázuri
通讯作者：
M. Landázuri
BMP 信号传导是睫状体发育所必需的。
DOI：
10.1242/dev.129.19.4435
发表时间：
2002
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Zhao,Shulei;Chen,Qin;Hung,Fang-Cheng;Overbeek,PaulA
通讯作者：
Overbeek,PaulA
影响因子：
1.8
作者：
Klein, B E;Klein, R;Moss, S E
通讯作者：
Moss, S E