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Oct3/4 在 5-Fu 处理后大鼠肺泡上皮损伤修复过程中的表达及作用。

Expression and Role of Oct3/4 in Injury-Repair Process of Rat Alveolar Epithelium after 5-Fu Treatment.

机构信息

Department of Pathology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.

Department of Thoracic Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.

出版信息

Biomed Res Int. 2017;2017:3856839. doi: 10.1155/2017/3856839. Epub 2017 Aug 29.

Abstract

OBJECTIVE

We aimed to investigate how the embryonic stem cell-related gene Oct3/4 changes during the injury-repair process of distal pulmonary epithelium induced by 5-fluorouracil (5-Fu).

METHODS

We have developed the lung injury model induced by 5-Fu and observed the dynamic changes of Oct3/4 by indirect immunofluorescence, Western blot, and quantitative real-time PCR. Immunofluorescence double staining was used to compare the positions of Oct3/4(+) cells and other reported alveolar epithelial stem cells.

RESULTS

Oct3/4(+) cells were not found in normal rat lung epithelial cells. However, after treatment with 5-Fu, Oct3/4(+) cells appeared at 12 h, reached the peak at 24 h, then decreased at 48 h, and eventually disappeared at 72 h. Oct3/4 was localized in the nucleus. We found that the sites of Clara cell secretory protein and surfactant protein-C dual positive cells were apparently different from Oct3/4(+) cells.

CONCLUSIONS

Our results revealed that, in rat alveolar epithelium, expression of Oct3/4 could be induced after treatment with 5-Fu, then decreased gradually, and was silenced following the alveolar epithelial differentiation. We hold that Oct3/4(+) cells are lung stem cells, which can provide new evidence for identification and isolation of lung epithelial stem cells.

摘要

目的

研究 5-氟尿嘧啶(5-Fu)诱导的远端肺上皮损伤修复过程中胚胎干细胞相关基因 Oct3/4 的变化。

方法

我们建立了 5-Fu 诱导的肺损伤模型,通过间接免疫荧光、Western blot 和实时定量 PCR 观察 Oct3/4 的动态变化。免疫荧光双重染色用于比较 Oct3/4(+)细胞与其他报道的肺泡上皮干细胞的位置。

结果

正常大鼠肺上皮细胞中未发现 Oct3/4(+)细胞。然而,用 5-Fu 处理后,12 h 出现 Oct3/4(+)细胞,24 h 达到高峰,48 h 下降,72 h 最终消失。Oct3/4 定位于细胞核。我们发现 Clara 细胞分泌蛋白和表面活性蛋白-C 双阳性细胞的部位与 Oct3/4(+)细胞明显不同。

结论

我们的结果表明,在大鼠肺泡上皮中,用 5-Fu 处理后可诱导表达 Oct3/4,然后逐渐减少,在肺泡上皮分化后沉默。我们认为 Oct3/4(+)细胞是肺干细胞,可为肺上皮干细胞的鉴定和分离提供新的证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae88/5602623/791004a5b0d7/BMRI2017-3856839.001.jpg

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