Identification and Characterization of Rat RhoA Gene Promoter

被引:8
作者
Chiba, Yoshihiko [1 ]
Goto, Kumiko [1 ]
Matsusue, Kimihiko [2 ]
Kimura, Shioko [3 ]
Misawa, Miwa [1 ]
机构
[1] Hoshi Univ, Sch Pharm, Dept Pharmacol, Tokyo 1428501, Japan
[2] Fukuoka Univ, Fac Pharmaceut Sci, Fukuoka 8140180, Japan
[3] NCI, Lab Metab, NIH, Bethesda, MD 20814 USA
关键词
RhoA; transcriptional regulation; bronchial smooth muscle; BRONCHIAL SMOOTH-MUSCLE; MEDIATED CA2+ SENSITIZATION; INHIBITOR; ASTHMA; INTERLEUKIN-13; KINASE; CELLS; JAK2;
D O I
10.1254/jphs.09346SC
中图分类号
R9 [药学];
学科分类号
100702 [药剂学];
摘要
RhoA upregulation has been suggested in bronchial smooth muscles (BSMs) of asthmatic rats. Here, we cloned/characterized the 5'-promoter region of the rat rhoA. A transcription-initiation site was identified at 66-bp upstream of the reference sequence, GenBank-BC061732. Luciferase assay using interleukin-13 (IL-13) stimulated cells revealed a significant promoter activity at 238- to 166-bp upstream of the transcription-initiation site, which contains a signal transducer and activation of transcription (STAT) 6 binding region. The IL-13 induced increase in luciferase activity was inhibited by a STAT6 inhibitor, AS 1517499, or a Janus kinases (JAKs) inhibitor, JAK Inhibitor-1, but not by tyrphostin-AG490, WHI-P131, or tyrphostin-AG9 (selective JAK2, JAK3, and Tyk2 inhibitors, respectively). Thus, rat BSM rhoA expression may have causal relation to the IL-13-JAK1-STAT6 signaling.
引用
收藏
页码:467 / 472
页数:6
相关论文
共 17 条
[1]
Cytokine profiles of BAL T cells and T-cell clones obtained from human asthmatic airways after local allergen challenge [J].
Bodey, KJ ;
Semper, AE ;
Redington, AE ;
Madden, J ;
Teran, LM ;
Holgate, ST ;
Frew, AJ .
ALLERGY, 1999, 54 (10) :1083-1093
[2]
Augmented acetylcholine-induced, Rho-mediated Ca2+ sensitization of bronchial smooth muscle contraction in antigen-induced airway hyperresponsive rats [J].
Chiba, Y ;
Takada, Y ;
Miyamoto, S ;
Mitsui-Saito, M ;
Karaki, H ;
Misawa, M .
BRITISH JOURNAL OF PHARMACOLOGY, 1999, 127 (03) :597-600
[3]
Involvement of RhoA-mediated Ca2+ sensitization in antigen-induced bronchial smooth muscle hyperresponsiveness in mice -: art. no. 4 [J].
Chiba, Y ;
Ueno, A ;
Shinozaki, K ;
Takeyama, H ;
Nakazawa, S ;
Sakai, H ;
Misawa, M .
RESPIRATORY RESEARCH, 2005, 6 (3-5)
[4]
Chiba Yoshihiko, 2003, Journal of Smooth Muscle Research, V39, P221, DOI 10.1540/jsmr.39.221
[5]
A Novel STAT6 Inhibitor AS1517499 Ameliorates Antigen-Induced Bronchial Hypercontractility in Mice [J].
Chiba, Yoshihiko ;
Todoroki, Michiko ;
Nishida, Yuichi ;
Tanabe, Miki ;
Misawa, Miwa .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2009, 41 (05) :516-524
[6]
Interleukin-13 Augments Bronchial Smooth Muscle Contractility with an Up-Regulation of RhoA Protein [J].
Chiba, Yoshihiko ;
Nakazawa, Shuji ;
Todoroki, Michiko ;
Shinozaki, Koji ;
Sakai, Hiroyasu ;
Misawa, Miwa .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2009, 40 (02) :159-167
[7]
IL-13 induces translocation of NF-κB in cultured human bronchial smooth muscle cells [J].
Goto, Kumiko ;
Chiba, Yoshihiko ;
Misawa, Miwa .
CYTOKINE, 2009, 46 (01) :96-99
[8]
Janus kinase 3 regulates interleukin 2-induced mucosal wound repair through tyrosine phosphorylation of villin [J].
Kumar, Narendra ;
Mishra, Jayshree ;
Narang, Vishal S. ;
Waters, Christopher M. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (42) :30341-30345
[9]
RhoA/Rho-Kinase as a Therapeutic Target in Asthma [J].
Kume, Hiroaki .
CURRENT MEDICINAL CHEMISTRY, 2008, 15 (27) :2876-2885
[10]
Synthesis and evaluation of 2-{[2-(4-hydroxyphenyl)-ethyl] amino} pyrimidine-5-carboxamide derivatives as novel STAT6 inhibitors [J].
Nagashima, Shinya ;
Yokota, Masaki ;
Nakai, Ei-ichi ;
Kuromitsu, Sadao ;
Ohga, Keiko ;
Takeuchi, Makoto ;
Tsukamoto, Shin-ichi ;
Ohta, Mitsuaki .
BIOORGANIC & MEDICINAL CHEMISTRY, 2007, 15 (02) :1044-1055