Involvement of gp130-mediated signaling in pressure overload-induced activation of the JAK/STAT pathway in rodent heart.
Previously, we showed that the JAK/STAT pathway was activated in pressure-overloaded rat heart, and that angiotensin II was partially involved in this activation. The present study was designed to investigate whether gp130-mediated signaling is involved in this activation, and if so, which interleukin (IL)-6 family cytokine is involved. Pressure overload was produced by ligation of the abdominal aorta of Wistar rats or ICR mice. IP-Western blot was performed to detect tyrosine phosphorylation of STATs, gp130, and the association of gp130 with JAK kinases. The serum concentration of IL-6 was measured by enzyme-linked immunosorbent assay. Expression of IL-6, IL-11, leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), oncostatin M (OSM), and cardiotrophin-1 (CT-1) mRNA was quantitated. After pressure overload, rapid phosphorylation of STAT1 and STAT3 was observed at 5 min, STAT1 was rephosphorylated at 60 min, and intense phosphorylation of STAT3 was observed at 60 min. Both the phosphorylation of gp130 and the association of gp130 with JAK1 and JAK2 were increased after pressure overload. IL-6 was significantly increased by two-fold in the pressure-overloaded rats. Only CT-1 mRNA expression could be detected by Northern blot, and it increased after pressure overload. Reverse transcription-polymerase chain reaction revealed that IL-6 mRNA expression was increased 9.5-fold. IL-11, LIF, CNTF, and OSM expression were unaffected by pressure overload. These results suggested that gp130-mediated signaling was involved in the pressure overload-induced activation of the JAK/STAT pathway, and that IL-6 and CT-1 might be involved in this activation.
Pan
J
J
Department of Internal Medicine, Keio University, Tokyo, Japan.
Fukuda
K
K
Kodama
H
H
Sano
M
M
Takahashi
T
T
Makino
S
S
Kato
T
T
Manabe
T
T
Hori
S
S
Ogawa
S
S
D000818:Animals; D015153:Blotting, Western; D006332:Cardiomegaly / Q000503:physiopathology*; D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D015850:Interleukin-6 / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D009206:Myocardium / Q000378:metabolism*; D010766:Phosphorylation; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism
D016207:Cytokines; D015850:Interleukin-6; D012333:RNA, Messenger; D014443:Tyrosine; C092073:cardiotrophin 1