UGRP1, a Uteroglobin/Clara Cell Secretory Protein-Related Protein, Is a Novel Lung-Enriched Downstream Target Gene for the T/EBP/NKX2.1 Homeodomain Transcription Factor

AhR is an environmental response gene that mediates cellular responses to a variety of xenobiotic compounds that frequently function as AhR ligands. Many AhR ligands are classified as carcinogens or pro-carcinogens. Thus, AhR itself acts as a major mediator of the carcinogenic effect of many xenobiotics in vivo. In this concise review, mechanisms by which AhR trans-activates downstream target gene expression, modulates immune responses, and mediates malignant transformation and tumor development are discussed. Moreover, activation of AhR by post-translational modifications and crosstalk with other transcription factors or signaling pathways are also summarized.

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Abstract 355: Exercise Prevents Doxorubicin-induced Cardiotoxicity via Targeting Microrna-669a-5p in Mice

Circulation Research ◽

10.1161/res.117.suppl_1.355 ◽

2015 ◽

Vol 117 (suppl_1) ◽

Author(s):

Yihua Bei ◽

Jiahong Xu ◽

Tianzhao Xu ◽

Ping Chen ◽

Lin Che ◽

...

Keyword(s):

Protective Effect ◽

Target Gene ◽

Contractile Function ◽

Cardiac Contractile Function ◽

Downstream Target ◽

Cardiac Contractile ◽

Downstream Target Gene ◽

Cardiac Ejection Fraction ◽

Response To Exercise ◽

Fractional Shortening

Doxorubicin (Dox)-induced cardiotoxicity, usually associated with increased oxidative stress, myofibrillar deterioration, and impaired cardiac contractile function, is a serious complication of antitumor therapy which may not be detected for many years. Growing evidence indicates that the regulation of cardiac microRNA (miRNA, miR) in response to exercise is essentially involved in the protective effect of exercise in the treatment of cardiovascular diseases. However, it is largely unknown whether and how exercise could prevent Dox-induced cardiotoxicity via regulating miRNA biology. In the current study, C57BL/6 mice were either subjected to a 3-week swimming program or remained sedentary. Mice were then treated with Dox (ip. 4 mg/kg/week for 4 weeks) to induce cardiotoxicity. Our data demonstrated that Dox resulted in marked reduction of cardiac ejection fraction (EF, %) and fractional shortening (FS, %) as measured by echocardiography. Interestingly, exercise significantly improved cardiac EF (%) and FS (%) in Dox-treated mice, indicating the protective effect of exercise in Dox-induced cardiotoxicity. Then, we performed microarray analysis (Affymetrix 3.0) showing that miR-27a-5p, miR-34b-3p, miR-185-3p, miR-203-3p, miR-669a-5p, miR-872-3p, and let-7i-3p were significantly reduced, while miR-2137 was increased in the hearts of exercised Dox-treated mice versus sedentary Dox-treated mice (FC(abs)>1.5, p<0.05). Using qRT-PCR, we further verified that miR-669a-5p was reduced by exercise training in Dox-treated mice. These data reveal that miR-669a-5p might be a potential miRNA mimicking the benefit of exercise in Dox-induced cardiotoxicity. Further study is needed to clarify the functional effect of miR-669a-5p and to identify its downstream target gene that contributes to the prevention and treatment of Dox-induced cardiotoxicity.

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Structure and Regulation of the Murine Clara Cell Secretory Protein Gene

Genomics ◽

10.1006/geno.1994.1123 ◽

1994 ◽

Vol 20 (1) ◽

pp. 27-35 ◽

Cited By ~ 31

Author(s):

Barry R. Stripp ◽

Jacquelyn A. Huffman ◽

Robert J. Bohinski

Keyword(s):

Protein Gene ◽

Secretory Protein ◽

Clara Cell ◽

Clara Cell Secretory Protein

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Regulation of a dpp target gene in the Drosophila embryo

Development ◽

10.1242/dev.124.2.303 ◽

1997 ◽

Vol 124 (2) ◽

pp. 303-311 ◽

Cited By ~ 3

Author(s):

J. Rusch ◽

M. Levine

Keyword(s):

Target Gene ◽

Fusion Gene ◽

Drosophila Embryo ◽

Specific Expression ◽

Downstream Target ◽

Embryonic Tissues ◽

Posterior Midgut ◽

Downstream Target Gene ◽

Genetic Epistasis ◽

Vp16 Fusion

In Drosophila, two TGF-beta growth factors, dpp and screw, function synergistically to subdivide the dorsal ectoderm into two embryonic tissues, the amnioserosa and dorsal epidermis. Previous studies have shown that peak dpp activity is required for the localized expression of zerknullt (zen), which encodes a homeodomain transcription factor. We present evidence that zen directly activates the amnioserosa-specific expression of a downstream target gene, Race (Related to angiotensin converting enzyme). A 533 bp enhancer from the Race promoter region is shown to mediate selective expression in the amnioserosa, as well as the anterior and posterior midgut rudiments. This enhancer contains three zen protein binding sites, and mutations in these sites virtually abolish the expression of an otherwise normal Race-lacZ fusion gene in the amnioserosa, but not in the gut. Genetic epistasis experiments suggest that zen is not the sole activator of Race, although a hyperactivated form of zen (a zen-VP16 fusion protein) can partially complement reduced levels of dpp activity. These results suggest that dpp regulates multiple transcription factors, which function synergistically to specify the amnioserosa.

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