Transforming growth factor β1‐mediated inhibition of smooth muscle cell proliferation is associated with a late G1 cell cycle arrest

Journal of Cellular Physiology - Tập 156 Số 1 - Trang 48-55 - 1993
Kumar B. Reddy1, Philip H. Howe1
1Department of Cell Biology (NC‐1), Cleveland Clinic Research Foundation, Cleveland, Ohio 44195

Tóm tắt

AbstractThe effect of transforming growth factor β1 (TGFβ1) on the proliferative response of aortic smooth muscle cells (SMC) in vitro was investigated. TGFβ1 substantially inhibited the growth of human and bovine SMC. Rapidly growing SMC and quiescent serum‐stimulated SMC were inhibited by TGFβ1 with an ID50 of approximately 0.5 ng/ml and maximal inhibition was observed at 10 ng/ml TGFβ1. In the presence of TGFβ1, quiescent serum‐stimulated SMC progress into the G1 phase of the cell cycle, but become reversibly arrested at a point temporally located 1–2 hours from S phase. Release from this late G1 TGFβ1 arrest point results in S phase entry within 2 hours. Associated with this inhibitory effect is a decrease in the histone H1 kinase activity of p34cdc2 protein kinase while TGFβ1 has no effect on the transcription or translation of p34cdc2. Under these growth inhibitory conditions, TGFβ1 is still capable of upregulating the expression of fibronectin mRNA. These results suggest that TGFβ1 growth inhibition in SMC is associated with the regulation of p34cdc2 activity in late G1. © 1993 Wiley‐Liss, Inc.

Từ khóa


Tài liệu tham khảo

10.1083/jcb.102.4.1217

10.1016/0092-8674(90)90448-N

10.1161/01.ATV.11.4.892

10.1073/pnas.86.12.4362

10.1016/0003-2697(87)90021-2

10.1002/j.1460-2075.1987.tb02449.x

10.1016/S0021-9258(18)83724-3

Goustin A. S., 1986, Growth factors and cancer, Cancer Res., 46, 1015

10.1002/jcp.1041280226

Howe P. H., 1989, Regulation of transforming growth factor β1 action by multiple transducing pathways: Evidence for both G protein‐dependent and‐independent signaling, Cancer Res., 49, 6024

10.1128/MCB.11.3.1185

10.1016/S0021-9258(17)35666-1

10.1002/jcp.1041500203

10.1016/0092-8674(90)90251-9

10.1038/327031a0

10.1002/j.1460-2075.1991.tb05006.x

10.1073/pnas.83.8.2453

Liau G., 1989, Regulation of extracellular matrix RNA levels in cultured smooth muscle cells. Relationship to cellular quiescence, J. Biol. Chem., 264, 10315, 10.1016/S0021-9258(18)81802-6

10.1083/jcb.105.1.465

10.1172/JCI115393

10.1073/pnas.83.21.8206

10.1128/MCB.6.5.1679

10.1016/0021-9150(91)90085-H

10.1016/S0006-291X(88)80047-0

10.1016/0092-8674(90)90188-K

10.1083/jcb.50.1.172

10.1016/0092-8674(83)90175-7

10.1073/pnas.82.12.4147

10.1016/0006-291X(89)91759-2

10.1002/jcp.1041430319

10.1128/MCB.11.10.4952

Thông tin
Thông tin xuất bản

Journal of Cellular Physiology

Tập 156 Số 1

48-55

Thông tin tác giả