Bcl-2 sustains increased mucous and epithelial cell numbers in metaplastic airway epithelium
Bcl-2 sustains increased mucous and epithelial cell numbers in metaplastic airway epithelium
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DOI：
10.1164/rccm.200408-1108oc
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发表时间：
2005-04-01
影响因子：
24.7
通讯作者：
Tesfaigzi, Y
中科院分区：
文献类型：
--
作者：
Harris, JF;Fischer, MJ;Tesfaigzi, Y
凋亡抑制因子Bcl-2在LPS诱导的大鼠气道化生杯状细胞中表达。本研究调查了Bcl-2在囊性纤维化患者气道粘液细胞中的表达，并在大鼠和小鼠中测试其表达是否负责维持化生粘液细胞。与无疾病的对照受试者或患有其他疾病的受试者相比，患有囊性纤维化的人中表达Bcl-2的粘液细胞的百分比显著较高。在LPS灌注的F344/N大鼠中，Bcl-2阳性粘液细胞的百分比在杯状细胞化生消退之前降低至背景水平。腹腔注射反义寡核苷酸可显著降低大鼠鼻和肺气道上皮Bcl-2表达和杯状细胞化生。相反，与野生型小鼠相比，在转基因小鼠中通过金属硫蛋白启动子持续表达Bcl-2导致增加LPS诱导的杯状细胞化生超过8天。这些研究表明，Bcl-2表达维持各种物种中的杯状细胞化生，上皮细胞数量与杯状细胞数量的调节直接相关，下调Bcl-2表达可减少杯状细胞化生。
Bcl-2, an inhibitor of apoptosis, is expressed in LPS-induced metaplastic goblet cells of rat airways. The present study investigated expression of Bcl-2 in airway mucous cells of persons with cystic fibrosis and tested in rats and mice whether its expression is responsible for sustaining metaplastic mucous cells. A significantly higher percentage of mucous cells expressed Bcl-2 in humans with cystic fibrosis compared with control subjects with no disease or subjects with other diseases. In LIPS-instilled F344/N rats, the percentage of Bcl-2-positive mucous cells was decreased to background levels before the resolution of goblet cell metaplasia. Furthermore, intraperitoneal injection of rats with antisense oligonucleoticles significantly reduced Bcl-2 expression and goblet cell metaplasia in nasal and pulmonary airway epithelia in rats. In contrast, sustained expression of Bcl-2 in transgenic mice by a metallothionein promoter caused increased LPS-incluced goblet cell metaplasia over 8 days compared with wild-type mice. These studies demonstrate that BcI-2 expression sustains goblet cell metaplasia in various species, that epithelial cell numbers are directly linked to the regulation of the numbers of goblet cells, and that downregulating Bcl-2 expression reduces goblet cell metaplasia.