Intracellular insulin-like growth factor-1 induces Bcl-2 expression in airway epithelial cells.
Intracellular insulin-like growth factor-1 induces Bcl-2 expression in airway epithelial cells.
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DOI：
10.4049/jimmunol.1102673
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发表时间：
2012-05-01
期刊：
影响因子：
--
通讯作者：
Tesfaigzi Y
中科院分区：
文献类型：
--
作者：
Chand HS;Harris JF;Mebratu Y;Chen Y;Wright PS;Randell SH;Tesfaigzi Y
Bcl-2是一种促生存蛋白，在发育和修复过程中调节程序性细胞死亡，并且当细胞增殖失调时可以致癌。本研究调查了哪些因素调节气道上皮细胞Bcl-2的表达，并确定了参与的途径。通过激光显微切割捕获的气道上皮细胞mRNA的微阵列分析显示，与对照组相比，IL-1β和IGF-1的表达增加与诱导的Bcl-2表达一致。用IL-1β和IGF-1处理培养的气道上皮细胞，通过增加Bcl-2 mRNA的稳定性诱导Bcl-2表达，而启动子活性没有明显变化。使用shRNA沉默IGF-1表达表明细胞内（IC）-IGF-1增加Bcl-2表达。阻断EGFR或IGF-1 R活化也抑制IC-IGF-1，并消除Bcl-2诱导。在暴露于LPS或香烟烟雾的小鼠以及囊性纤维化和慢性支气管炎患者的气道上皮细胞中观察到IC-IGF-1和Bcl-2的诱导表达和共定位，但在相应的对照中没有观察到。这些研究表明，IC-IGF-1通过IGF-1 R和EGFR途径诱导上皮细胞中Bcl-2的表达，靶向IC-IGF-1可能有利于治疗慢性气道疾病。
Bcl-2, a prosurvival protein, regulates programmed cell death during development and repair processes, and can be oncogenic when cell proliferation is deregulated. The present study investigated what factors modulate Bcl-2 expression in airway epithelial cells and identified the pathways involved. Microarray analysis of mRNA from airway epithelial cells captured by laser microdissection showed that increased expression of IL-1β and IGF-1 coincided with induced Bcl-2 expression compared to controls. Treatment of cultured airway epithelial cells with IL-1β and IGF-1 induced Bcl-2 expression by increasing Bcl-2 mRNA stability with no discernible changes in promoter activity. Silencing the IGF-1 expression using shRNA showed that intracellular (IC)-IGF-1 was increasing Bcl-2 expression. Blocking EGFR or IGF-1R activation also suppressed IC-IGF-1, and abolished the Bcl-2 induction. Induced expression and co-localization of IC-IGF-1 and Bcl-2 were observed in airway epithelial cells of mice exposed to LPS or cigarette smoke and of patients with cystic fibrosis and chronic bronchitis but not in the respective controls. These studies demonstrate that IC-IGF-1 induces Bcl-2 expression in epithelial cells via IGF-1R and EGFR pathways, and targeting IC-IGF-1 could be beneficial to treat chronic airway diseases.
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影响因子：
24.3
作者：
Kohri, K;Ueki, IF;Nadel, JA
通讯作者：
Nadel, JA
影响因子：
8
作者：
Heckman, CA;Wheeler, MA;Boxer, LM
通讯作者：
Boxer, LM
影响因子：
29.4
作者：
Kanai, M;Konda, Y;Chiba, T
通讯作者：
Chiba, T
DOI：
10.1164/rccm.200408-1108oc
发表时间：
2005-04-01
影响因子：
24.7
作者：
Harris, JF;Fischer, MJ;Tesfaigzi, Y
通讯作者：
Tesfaigzi, Y
影响因子：
64.5
作者：
BAKHSHI, A;JENSEN, JP;KORSMEYER, SJ
通讯作者：
KORSMEYER, SJ