TGF-BETA INDUCES BIMODAL PROLIFERATION OF CONNECTIVE-TISSUE CELLS VIA COMPLEX CONTROL OF AN AUTOCRINE PDGF LOOP
TGF-BETA INDUCES BIMODAL PROLIFERATION OF CONNECTIVE-TISSUE CELLS VIA COMPLEX CONTROL OF AN AUTOCRINE PDGF LOOP
复制标题
DOI：
10.1016/0092-8674(90)90448-n
复制
发表时间：
1990-11-02
期刊：
影响因子：
64.5
通讯作者：
ROSS, R
中科院分区：
文献类型：
--
作者：
BATTEGAY, EJ;RAINES, EW;ROSS, R
转化生长因子-β（TGF-β）作为生长抑制剂，但它可以刺激增殖; 1- 2fg/细胞的TGF-β 1促进密集和稀疏培养的平滑肌细胞（SMC）的最大增殖，而更高的量刺激性较小。这种双峰响应不限于SMC，如TGF-β。在人成纤维细胞和软骨细胞中诱导类似的反应。诱导最大增殖的每个细胞的TGF-β 1的量对于密集和稀疏SMC是相同的。在低浓度的TGF-β下，与PDGF引起的相比，DNA合成延迟10-12小时。在24小时时在培养基中检测到PDGF-AA，并且抗PDGF IgG阻断DNA合成。在较高浓度下，TGF-β 1降低PDGF受体α的转录物和表达。亚单位。因此，TGF-β。通过刺激自分泌PDGF-AA分泌，在低浓度下诱导结缔组织细胞增殖，在较高浓度的TGF-β，通过下调PDGF受体α而降低。亚基和可能通过直接生长抑制。
Transforming growth factor-.beta. (TGF-.beta.) acts as a growth inhibitor, yet it can stimulate proliferation; 1-2 fg/cell of TGF-.beta.1 elicits maximal proliferation of dense and sparse cultured smooth muscle cells (SMCs), whereas higher amounts are less stimulatory. This bimodal response is not limited to SMCs, as TGF-.beta. induces a similar response in human fibroblasts and chondrocytes. The amount of TGF-.beta.1 per cell that induces maximal proliferation is identical for dense and sparse SMCs. At low concentrations of TGf-.beta., there is a 10-12 hr delay in DNA synthesis compared with that elicited by PDGF. PDGF-AA is detected in the culture medium at 24 h, and anti-PDGF IgG blocks DNA synthesis. At higher concentrations, TGF-.beta.1 decreases transcripts and expression of PDGF receptor .alpha. subunits. Hence, TGF-.beta. induces proliferation of connective tissue cells at low concentrations by stimulating autocrine PDGF-AA secretion, which at higher concentrations of TGF-.beta., is decreased by down-regulation of PDGF receptor .alpha. subunits and perhaps by direct growth inhibition.