Cell cycle in alveolar epithelial type II cells: integration of Matrigel and KGF
Cell cycle in alveolar epithelial type II cells: integration of Matrigel and KGF
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DOI：
10.1152/ajplung.1997.273.3.l572
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发表时间：
1997-09-01
影响因子：
4.9
通讯作者：
Warburton, D
中科院分区：
文献类型：
--
作者：
Buckley, S;Driscoll, B;Warburton, D
肺泡上皮II型细胞（AEC 2）响应肽生长因子和细胞外基质信号的细胞周期控制的调节还没有得到很好的理解。在此，我们已经确定，在Engelbreth-Holm-Swarm生物基质上原代培养的成年大鼠AEC 2中，（Matrigel）在角质形成细胞生长因子存在下，关键细胞周期控制元件（包括细胞周期蛋白A和D以及细胞周期蛋白依赖性激酶（cdk）1和4）的表达增加，并且视网膜母细胞瘤蛋白（pRb）磷酸化也增加，与在塑料上培养的细胞相比，p53和cdk抑制剂（cdkis）p21（WAF 1/CIP 1）和p27（KIP-1）的表达相应降低。基质胶生物基质-KGF培养条件也与增强的增殖反应相关，如通过荧光激活细胞分选仪分析、胸苷掺入DNA和增殖细胞核抗原表达所测量的。这种增强的增殖既不发生在基质胶生物基质的可溶性提取物中，也不发生在其他简单的生物基质中。我们得出结论，协调诱导的关键细胞周期蛋白和cdks，与随之而来的抑制关键负细胞周期调节剂，发生在AEC 2基质中的KGF的存在下。我们推测，细胞周期蛋白和cdk激活和cdki抑制之间的平衡，在AEC 2的服务整合的生物基质和KGF信号对pRb磷酸化的综合影响，从而控制通过S期的细胞周期的过境。相反，AEC 2在G（1）期静止时表达高水平的cdkis和p53。后一个发现可以解释正常成人AEC 2在体内的静止状态。
The regulation of cell cycle control in alveolar epithelial type II cells (AEC2) in response to peptide growth factors and extracellular matrix signals is not well understood. Herein, we have determined that, in adult rat AEC2 in primary culture on Engelbreth-Holm-Swarm biomatrix (Matrigel) in the presence of keratinocyte growth factor, the expression of key cell cycle control elements, including cyclins A and D and cyclin-dependent kinases (cdk) 1 and 4, is increased and that retinoblastoma protein (pRb) phosphorylation is also increased, with a corresponding decrease in the expression of p53 and the cdk inhibitors (cdkis) p21(WAF1/CIP1) and p27(KIP-1) compared with cells cultured on plastic. The Matrigel biomatrix-KGF culture conditions were also associated with an enhanced proliferative response, as measured by fluorescent-activated cell sorter analysis, thymidine incorporation into DNA, and proliferating cell nuclear antigen expression. This enhanced proliferation occurred with neither a soluble extract of Matrigel biomatrix nor with other simple biological matrices. We conclude that coordinated induction of key cyclins and cdks, with the concomitant suppression of key negative cell cycle regulators, occurs in AEC2 on Matrigel biomatrix in the presence of KGF. We speculate that the balance between cyclin and cdk activation and cdki suppression in AEC2 serves to integrate the combined influences of biomatrix and KGF signaling on pRb phosphorylation, thereby controlling transit through S phase of the cell cycle. Conversely, AEC2 express high levels of cdkis and p53 at rest in G(1) phase. The latter finding may explain the quiescent state of normal adult AEC2 in vivo.