Different global gene expression profiles in benzo[a]pyrene- and dioxin-treated vascular smooth muscle cells of AHR-knockout and wild-type mice.
Different global gene expression profiles in benzo[a]pyrene- and dioxin-treated vascular smooth muscle cells of AHR-knockout and wild-type mice.
复制标题
DOI：
10.1385/ct:4:1:47
复制
发表时间：
2004-01-01
影响因子：
3.2
通讯作者：
Tomlinson, Craig R
中科院分区：
文献类型：
--
作者：
Karyala, Saikumar;Guo, Junhai;Tomlinson, Craig R
苯并[a]芘（B[a]P）和2,3,7,8-四氯二苯并-对二恶英（TCDD）是芳烃受体（AHR）的有效配体。采用高密度寡核苷酸微阵列技术对小鼠主动脉野生型和Ahr（-/-）血管平滑肌细胞（SMCs）进行基因表达谱分析。为了确定除AHR外是否还有其他信号通路参与B[a]P代谢，我们将野生型和AHR敲除（AHR (-/-)） SMCs暴露于B[a]P。以tgf - β 2和IGF-1为代表的两个信号通路被确定为AHR细胞对B反应的替代途径的潜在候选者[a]P。野生型SMCs对B[a]P和TCDD的反应类似于对一组已知对活化AHR有反应的常见基因的调节（例如，谷氨酰胺s -转移酶）。然而，野生型SMCs以一种涉及许多其他基因的方式作出反应，这表明当SMCs暴露于AHR的两种经典诱导剂时，可能涉及非常不同的细胞反应。相比之下，Ahr（-/-）细胞中更多的基因对B[a]P和TCDD有相似的反应，包括Cyp1b1，而不是不同的反应，这表明消除Ahr对于研究对B[a]P和TCDD有反应的潜在替代细胞机制是有效的。
Benzo[a]pyrene (B[a]P) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are potent ligands for the aryl hydrocarbon receptor (AHR). High-density oligonucleotide microarrays were used to generate global gene expression profiles of wild-type and Ahr(-/-) vascular smooth muscle cells (SMCs) from mouse aorta. To determine whether there are signaling pathways other than the AHR involved in B[a]P metabolism, wild-type and AHR knockout (Ahr(-/-) SMCs were exposed to B[a]P. Two signaling pathways, represented by TGF-beta2 and IGF-1, were identified as potential candidates of an AHR alternate pathway for cells to respond to B[a]P. The wild-type SMCs responded similarly to B[a]P and TCDD in the regulation of a small set of common genes known to respond to the activated AHR (e.g., glutamine S-transferase). However, wild-type SMCs responded in a way that involves many additional genes, suggesting that a very divergent cellular response may be involved when SMCs are exposed to the two classic inducers of the AHR. In contrast, many more genes in the Ahr(-/-) cells responded similarly to B[a]P and TCDD, including Cyp1b1, than responded differently, which indicates that eliminating the AHR is effective for investigating potential alternate cellular mechanisms that respond to B[a]P and TCDD.