Epidermal growth factor increases claudin-4 expression mediated by Sp1 elevation in MDCK cells. 2009

Akira Ikari, and Kosuke Atomi, and Ayumi Takiguchi, and Yasuhiro Yamazaki, and Masao Miwa, and Junko Sugatani
Department of Pharmaco-Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. ikari@u-shizuoka-ken.ac.jp

Epidermal growth factor (EGF) increases claudin-4 expression in Madin-Darby canine kidney (MDCK) cells. Here we examined what regulatory mechanisms are involved in the EGF-induced claudin-4 elevation. EGF transiently increased claudin-4 mRNA at 3h and persistently increased its protein for 24h without affecting claudin-1 expression. EGF increased p-ERK1/2 levels, which were inhibited by U0126, a MEK inhibitor. The exogenous expression of constitutively activated MEK increased claudin-4 expression. These results indicate that the activation of ERK1/2 is involved in the EGF-induced claudin-4 elevation. EGF increased Sp1 expression within 1h, which was inhibited by U0126. In immunocytochemistry, Sp1 was distributed in nucleus in control and the EGF-treated cells. The EGF-induced claudin-4 elevation was inhibited by mithramycin, a Sp1 inhibitor, and Sp1 small interfering RNA. We suggest that EGF activates a MEK/ERK pathway and increases Sp1 expression, resulting in an elevation of claudin-4 expression.

UI MeSH Term Description Entries
D008565 Membrane Proteins Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D004815 Epidermal Growth Factor A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form. EGF,Epidermal Growth Factor-Urogastrone,Urogastrone,Human Urinary Gastric Inhibitor,beta-Urogastrone,Growth Factor, Epidermal,Growth Factor-Urogastrone, Epidermal,beta Urogastrone
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D016329 Sp1 Transcription Factor Promoter-specific RNA polymerase II transcription factor that binds to the GC box, one of the upstream promoter elements, in mammalian cells. The binding of Sp1 is necessary for the initiation of transcription in the promoters of a variety of cellular and viral GENES. Transcription Factor, Sp1,Specificity Protein 1 Transcription Factor
D048052 Mitogen-Activated Protein Kinase 3 A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS. Extracellular Signal-Regulated Kinase 1,ERK1 Kinase,MAPK3 Mitogen-Activated Protein Kinase,Meiosis-Activated Myelin Basic Protein Kinase p44(mpk),Microtubule-Associated Protein-2 Kinase,PSTkinase p44mpk,Protein-Serine-Threonine Kinase p44(mpk),p44 MAPK,Extracellular Signal Regulated Kinase 1,Kinase, ERK1,Kinase, Microtubule-Associated Protein-2,MAPK3 Mitogen Activated Protein Kinase,Microtubule Associated Protein 2 Kinase,Mitogen Activated Protein Kinase 3,p44mpk, PSTkinase
D062506 Claudin-4 A claudin subtype that takes part in maintaining the barrier-forming property of TIGHT JUNCTIONS. Claudin-4 is found associated with CLAUDIN-8 in the KIDNEY COLLECTING DUCT where it may play a role in paracellular chloride ion reabsorption. Claudin4,Claudin 4
D019950 Mitogen-Activated Protein Kinase 1 A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms. Extracellular Signal-Regulated Kinase 2,MAP Kinase 2,Mitogen-Activated Protein Kinase 2,p42 MAP Kinase,p42 MAPK,p42(Mitogen-Activated Protein Kinase),MAPK1 Mitogen-Activated Protein Kinase,MAPK2 Mitogen-Activated Protein Kinase,p42(Mapk),p42(Mapk) Kinase,Extracellular Signal Regulated Kinase 2,MAP Kinase, p42,MAPK1 Mitogen Activated Protein Kinase,MAPK2 Mitogen Activated Protein Kinase,Mitogen Activated Protein Kinase 1,Mitogen Activated Protein Kinase 2
D034741 RNA, Small Interfering Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions. RNA, Scan,Repeat-Associated siRNA,Scan RNA,Small Scan RNA,Trans-Acting siRNA,siRNA,siRNA, Repeat-Associated,siRNA, Trans-Acting,Short Hairpin RNA,Short Interfering RNA,Small Hairpin RNA,Small Interfering RNA,scnRNA,shRNA,tasiRNA,Hairpin RNA, Short,Hairpin RNA, Small,Interfering RNA, Short,Interfering RNA, Small,RNA, Short Hairpin,RNA, Short Interfering,RNA, Small Hairpin,RNA, Small Scan,Repeat Associated siRNA,Scan RNA, Small,Trans Acting siRNA,siRNA, Repeat Associated,siRNA, Trans Acting

Related Publications

Akira Ikari, and Kosuke Atomi, and Ayumi Takiguchi, and Yasuhiro Yamazaki, and Masao Miwa, and Junko Sugatani
January 2017, PloS one,
Akira Ikari, and Kosuke Atomi, and Ayumi Takiguchi, and Yasuhiro Yamazaki, and Masao Miwa, and Junko Sugatani
July 2011, Oncogene,
Akira Ikari, and Kosuke Atomi, and Ayumi Takiguchi, and Yasuhiro Yamazaki, and Masao Miwa, and Junko Sugatani
June 1977, Biochemical and biophysical research communications,
Akira Ikari, and Kosuke Atomi, and Ayumi Takiguchi, and Yasuhiro Yamazaki, and Masao Miwa, and Junko Sugatani
April 2017, Oncotarget,
Akira Ikari, and Kosuke Atomi, and Ayumi Takiguchi, and Yasuhiro Yamazaki, and Masao Miwa, and Junko Sugatani
January 2015, PloS one,
Akira Ikari, and Kosuke Atomi, and Ayumi Takiguchi, and Yasuhiro Yamazaki, and Masao Miwa, and Junko Sugatani
January 2015, Journal of cellular physiology,
Akira Ikari, and Kosuke Atomi, and Ayumi Takiguchi, and Yasuhiro Yamazaki, and Masao Miwa, and Junko Sugatani
April 2002, American journal of physiology. Renal physiology,
Akira Ikari, and Kosuke Atomi, and Ayumi Takiguchi, and Yasuhiro Yamazaki, and Masao Miwa, and Junko Sugatani
July 2006, Arteriosclerosis, thrombosis, and vascular biology,
Akira Ikari, and Kosuke Atomi, and Ayumi Takiguchi, and Yasuhiro Yamazaki, and Masao Miwa, and Junko Sugatani
October 2011, Experimental and molecular pathology,
Akira Ikari, and Kosuke Atomi, and Ayumi Takiguchi, and Yasuhiro Yamazaki, and Masao Miwa, and Junko Sugatani
January 2023, Function (Oxford, England),
Copied contents to your clipboard!