Stanniocalcin-1 is induced by hypoxia inducible factor in rat alveolar epithelial cells.
Stanniocalcin-1 is induced by hypoxia inducible factor in rat alveolar epithelial cells.
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DOI：
10.1016/j.bbrc.2014.09.060
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发表时间：
2014-10-03
影响因子：
3.1
通讯作者：
Mason, Robert J.
中科院分区：
文献类型：
--
作者：
Ito, Yoko;Zernans, Rachel;Correll, Kelly;Yang, Ivana V.;Ahmad, Aftab;Gao, Bifeng;Mason, Robert J.
肺泡II型(ATII)细胞在空气-液体(A/L)界面培养时仍保持分化并表达表面活性物质蛋白。当在浸泡条件下培养时，ATII细胞去分化并改变其基因表达谱。我们以前已经证明，在浸没条件下，由于ATII细胞代谢导致的局灶性缺氧，基因表达受到缺氧诱导因子(HIF)信号的调节。在此，我们试图进一步确定在浸泡条件下培养的ATII细胞中基因表达的变化。我们对从A/L界面切换后培养24-48小时的大鼠ATII细胞的RNA进行了全基因组微阵列。我们发现HIF的基因表达发生了显著的变化，包括HIF靶基因stanniocalin-1(STc1)、酪氨酸羟基酶(Th)、烯醇化酶(Eno)2和基质金属蛋白酶(MMP13)的表达上调，我们通过RT-PCR验证了这些基因的上调。由于STc1是一种进化上高度保守的糖蛋白，具有抗炎、抗凋亡、抗氧化和伤口愈合等特性，在肺组织中广泛表达，我们进一步探讨了STc1在肺泡上皮细胞中的潜在功能。我们发现在低氧和低氧诱导的大鼠ATII细胞中，STC1被诱导，并且这种诱导迅速且可逆地发生。我们还发现，重组人STC_1(RhSTC_1)可促进肺泡上皮细胞(AEC)单层细胞运动，并形成延长的片状脂膜，但不能抑制内毒素所致的氧化损伤。我们还证实了STC1在人肺上皮细胞中受低氧和低氧诱导表达上调。在本研究中，我们发现包括STc1在内的几个HIF靶基因在AEC中被浸泡条件上调，STc1受缺氧和HIF的调节，这种调节是快速和可逆的，并且STc1在AEC单层中适度促进伤口愈合。但STC1对脂多糖刺激的大鼠血管内皮细胞氧化损伤无明显抑制作用。因此，ATII细胞在包括STC1在内的浸泡条件下基因表达的变化主要是由缺氧和HIF诱导的，这可能与我们理解肺泡上皮处于相对低氧状态的各种肺部疾病的发病机制有关。
Alveolar type II (ATII) cells remain differentiated and express surfactant proteins when cultured at an air-liquid (A/L) interface. When cultured under submerged conditions, ATII cells dedifferentiate and change their gene expression profile. We have previously shown that gene expression under submerged conditions is regulated by hypoxia inducible factor (HIF) signaling due to focal hypoxia resulting from ATII cell metabolism. Herein, we sought to further define gene expression changes in ATII cells cultured under submerged conditions. We performed a genome wide microarray on RNA extracted from rat ATII cells cultured under submerged conditions for 24–48 h after switching from an A/L interface. We found significant alterations in gene expression, including upregulation of the HIF target genes stanniocalcin-1 (STC1), tyrosine hydroxylase (Th), enolase (Eno) 2, and matrix metalloproteinase (MMP) 13, and we verified upregulation of these genes by RT-PCR. Because STC1, a highly evolutionarily conserved glycoprotein with anti-inflammatory, anti-apoptotic, anti-oxidant, and wound healing properties, is widely expressed in the lung, we further explored the potential functions of STC1 in the alveolar epithelium. We found that STC1 was induced by hypoxia and HIF in rat ATII cells, and this induction occurred rapidly and reversibly. We also showed that recombinant human STC1 (rhSTC1) enhanced cell motility with extended lamellipodia formation in alveolar epithelial cell (AEC) monolayers but did not inhibit the oxidative damage induced by LPS. We also confirmed that STC1 was upregulated by hypoxia and HIF in human lung epithelial cells. In this study, we have found that several HIF target genes including STC1 are upregulated in AECs by a submerged condition, that STC1 is regulated by hypoxia and HIF, that this regulation is rapidly and reversibly, and that STC1 enhances wound healing moderately in AEC monolayers. However, STC1 did not inhibit oxidative damage in rat AECs stimulated by LPS in vitro. Therefore, alterations in gene expression by ATII cells under submerged conditions including STC1 were largely induced by hypoxia and HIF, which may be relevant to our understanding of the pathogenesis of various lung diseases in which the alveolar epithelium is exposed to relative hypoxia.
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影响因子：
4.1
作者：
Emre, Yalin;Hurtaud, Corinne;Cassard-Doulcier, Anne-Marie
通讯作者：
Cassard-Doulcier, Anne-Marie
影响因子：
4.8
作者：
Aihara, Eitaro;Hentz, Courtney L.;Montrose, Marshall H.
通讯作者：
Montrose, Marshall H.
DOI：
10.1165/rcmb.2006-0037oc
发表时间：
2006-08-01
影响因子：
6.4
作者：
Chang, Yongsheng;Edeen, Karen;Mason, Robert J.
通讯作者：
Mason, Robert J.
影响因子：
6
作者：
Huang, Luping;Garcia, Gabriela;Sheikh-Hamad, David
通讯作者：
Sheikh-Hamad, David
DOI：
10.1165/ajrcmb.17.6.2858
发表时间：
1997-12-01
影响因子：
6.4
作者：
Alcorn, JL;Smith, ME;Mendelson, CR
通讯作者：
Mendelson, CR