Angiotensin II (Ang II) and transforming growth factor (TGF) β1 play a role in vascular remodeling in hypertension. In this process they may interact on various levels, including that of receptor regulation. This consideration prompted the present study on transcriptional regulation of TGF-β receptors by Ang II and TGF-β in vascular smooth muscle cells. Transcriptional expression of the components of the TGF-β system was demonstrated for TGF-β and for TGF-β receptors I, II, and III. As measured by quantitative reverse transcriptase polymerase chain reaction, TGF-β mRNA increased about 2.4-fold in the presence of 40 pM exogenous TGF-β. Ang II at 10–6 M increased TGF-β mRNA 2.5-fold compared to control cells (P<0.05). Ang II also significantly increased TGF-β protein concentration in the supernatant of confluent vascular smooth muscle cells. Ang II caused the induction of TGF-β, but short-term experiments showed TGF-β receptor II mRNA to be differentially regulated by Ang II and TGF-β; while TGF-β caused a 40% decrease in TGF-β receptor II mRNA after 4 h (P<0.05), Ang II caused an increase by about 70%. In contrast, both TGF-β and Ang II increased TGF-β receptor I mRNA to about 260% or 180% of controls (P<0.05). TGF-β effects were abrogated by coincubation with a TGF-β neutralizing antibody, and Ang II effects were abrogated by losartan, an AT-1 receptor antagonist. Coincubation of Ang II with the TGF-β neutralizing antibody did not inhibit the effect of Ang II, indicating that the short-term effects of Ang II on the expression of the TGF-β receptors are not mediated via TGF-β. Furthermore, Ang II stimulated DNA synthesis even in the presence of the TGF-β neutralizing antibody. In conclusion, this study indicates (a) that in vascular smooth muscle TGF-β receptors are regulated on the RNA level by TGF-β and Ang II, and (b) that Ang II dependent regulation of TGF-β receptors is at least partially independent of endogenous TGF-β. Stimulation of the transcriptional expression of TGF-β receptors by Ang II may increase sensitivity of vascular smooth muscle cells to TGF-β.
机构:
Nihon Univ, Dept Internal Med 2, Sch Med, Itabashi Ku, Tokyo 1738610, JapanNihon Univ, Dept Internal Med 2, Sch Med, Itabashi Ku, Tokyo 1738610, Japan
Fukuda, N
Hu, WY
论文数: 0引用数: 0
h-index: 0
机构:
Nihon Univ, Dept Internal Med 2, Sch Med, Itabashi Ku, Tokyo 1738610, JapanNihon Univ, Dept Internal Med 2, Sch Med, Itabashi Ku, Tokyo 1738610, Japan
Hu, WY
Kubo, A
论文数: 0引用数: 0
h-index: 0
机构:
Nihon Univ, Dept Internal Med 2, Sch Med, Itabashi Ku, Tokyo 1738610, JapanNihon Univ, Dept Internal Med 2, Sch Med, Itabashi Ku, Tokyo 1738610, Japan
Kubo, A
Kishioka, H
论文数: 0引用数: 0
h-index: 0
机构:
Nihon Univ, Dept Internal Med 2, Sch Med, Itabashi Ku, Tokyo 1738610, JapanNihon Univ, Dept Internal Med 2, Sch Med, Itabashi Ku, Tokyo 1738610, Japan
Kishioka, H
Satoh, C
论文数: 0引用数: 0
h-index: 0
机构:
Nihon Univ, Dept Internal Med 2, Sch Med, Itabashi Ku, Tokyo 1738610, JapanNihon Univ, Dept Internal Med 2, Sch Med, Itabashi Ku, Tokyo 1738610, Japan
Satoh, C
Soma, M
论文数: 0引用数: 0
h-index: 0
机构:
Nihon Univ, Dept Internal Med 2, Sch Med, Itabashi Ku, Tokyo 1738610, JapanNihon Univ, Dept Internal Med 2, Sch Med, Itabashi Ku, Tokyo 1738610, Japan
Soma, M
Izumi, Y
论文数: 0引用数: 0
h-index: 0
机构:
Nihon Univ, Dept Internal Med 2, Sch Med, Itabashi Ku, Tokyo 1738610, JapanNihon Univ, Dept Internal Med 2, Sch Med, Itabashi Ku, Tokyo 1738610, Japan
Izumi, Y
Kanmatsuse, K
论文数: 0引用数: 0
h-index: 0
机构:
Nihon Univ, Dept Internal Med 2, Sch Med, Itabashi Ku, Tokyo 1738610, JapanNihon Univ, Dept Internal Med 2, Sch Med, Itabashi Ku, Tokyo 1738610, Japan
机构:
Univ Manitoba, John Buhler Res Ctr, Fac Med, Dept Physiol, Winnipeg, MB R3E 3P4, CanadaUniv Manitoba, John Buhler Res Ctr, Fac Med, Dept Physiol, Winnipeg, MB R3E 3P4, Canada
Gawaziuk, J. P.
Ma, X.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Manitoba, John Buhler Res Ctr, Fac Med, Dept Physiol, Winnipeg, MB R3E 3P4, CanadaUniv Manitoba, John Buhler Res Ctr, Fac Med, Dept Physiol, Winnipeg, MB R3E 3P4, Canada
Ma, X.
Sheikh, F.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Manitoba, John Buhler Res Ctr, Fac Med, Dept Physiol, Winnipeg, MB R3E 3P4, CanadaUniv Manitoba, John Buhler Res Ctr, Fac Med, Dept Physiol, Winnipeg, MB R3E 3P4, Canada
Sheikh, F.
Cheng, Z-Q.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Manitoba, John Buhler Res Ctr, Fac Med, Dept Physiol, Winnipeg, MB R3E 3P4, CanadaUniv Manitoba, John Buhler Res Ctr, Fac Med, Dept Physiol, Winnipeg, MB R3E 3P4, Canada
Cheng, Z-Q.
Cattini, P. A.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Manitoba, John Buhler Res Ctr, Fac Med, Dept Physiol, Winnipeg, MB R3E 3P4, CanadaUniv Manitoba, John Buhler Res Ctr, Fac Med, Dept Physiol, Winnipeg, MB R3E 3P4, Canada
Cattini, P. A.
Stephens, N. L.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Manitoba, John Buhler Res Ctr, Fac Med, Dept Physiol, Winnipeg, MB R3E 3P4, CanadaUniv Manitoba, John Buhler Res Ctr, Fac Med, Dept Physiol, Winnipeg, MB R3E 3P4, Canada