Induction of uPA but not NF-IL3A by calcitonin is dependent on Erk1/2 phosphorylation in porcine renal cell line LLC-PK1.
Calcitonin (CT) is a polypeptide hormone and has a variety of functions including regulation of urinary calcium excretion. By using a cDNA subtraction hybridization method, we identified that NF-IL3A and urokinase-type plasminogen activator (uPA) genes were up-regulated by CT in porcine renal cell line LLC-PK1. CT-mediated induction of these genes was not inhibited by cycloheximide. These data suggest that these up-regulations are not induced by increased synthesis of regulating proteins; therefore, they are immediately response early (IE). We also found that CT treatment led to the phosphorylation of Erk1/2. We demonstrated that PD98059, a MEK1 inhibitor, inhibited CT-induced mRNA expressions of uPA, but had no obvious influence on the NF-IL3A induction. These results demonstrated the inductions of uPA by CT involve Erk1/2 phosphorylation. We provide the first evidence that NF-IL3A expression is up-regulated by CT. The present findings suggest that the transcriptions of the NF-IL3A and uPA could be induced by CT and might be important mediators of CT function in renal cells.
Nakamura
Misa
M
Department of Pathology, Wakayama Medical University, Kimiidera 811-1, Wakayama City, Wakayama 641-0012, Japan. marumisa@mail.wakayama-med.ac.jp
Yang
Qifeng
Q
Ozaki
Takashi
T
Nakamura
Yasushi
Y
Yamasaki
Hisashi
H
Mori
Ichiro
I
Kakudo
Kennichi
K
D000818:Animals; D002116:Calcitonin / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D051790:G-Box Binding Factors; D005786:Gene Expression Regulation / Q000187:drug effects; D017781:Genes, Immediate-Early / Q000187:drug effects; D018374:LLC-PK1 Cells / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D048369:MAP Kinase Kinase 1; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000096:biosynthesis; D013552:Swine; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification
D004791:Enzyme Inhibitors; D005419:Flavonoids; D051790:G-Box Binding Factors; D012333:RNA, Messenger; D015534:Trans-Activators; D002116:Calcitonin; D017346:Protein Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases; D014568:Urokinase-Type Plasminogen Activator; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one