Laminin and heparan sulfate proteoglycan mediate epithelial cell polarization in organotypic cultures of embryonic lung cells: evidence implicating involvement of the inner globular region of laminin beta 1 chain and the heparan sulfate groups of heparan
Laminin and heparan sulfate proteoglycan mediate epithelial cell polarization in organotypic cultures of embryonic lung cells: evidence implicating involvement of the inner globular region of laminin beta 1 chain and the heparan sulfate groups of heparan
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层粘连蛋白和硫酸乙酰肝素蛋白多糖介导胚胎肺细胞器官型培养物中的上皮细胞极化：证据表明层粘连蛋白β1链的内部球状区域和乙酰肝素的硫酸乙酰肝素基团参与其中
DOI：
10.1006/dbio.1996.0256
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发表时间：
1996
影响因子：
2.7
通讯作者：
He,L
中科院分区：
文献类型：
--
作者：
Schuger,L;Skubitz,AP;Gilbride,K;Mandel,R;He,L
细胞外基质尤其是基底膜在诱导细胞器官型重排中起着重要作用。这个过程包括细胞聚集、分成上皮和间充质成分、上皮细胞极化和管腔形成。在这项研究中，层粘连蛋白(LM)和硫酸肝素蛋白多糖(HSPG)这两种主要的BM成分联合作用，诱导了胚胎小鼠肺细胞的器质性重排。在没有添加LM/HSPG的情况下，细胞分为上皮室和间充质室，但没有发生上皮细胞极化和管腔形成。无论是LM还是HSPG都不能单独触发这一过程。合成肽F-9代表层粘连蛋白β1链内球区的氨基酸序列(RYVVLPRPVCFEKGMNYTVR)，当替代LM时，可诱导器官型细胞重排。外源性LM和F-9肽定位于器官型细胞培养的上皮-间充质界面，形成类BM结构，器官型细胞重排可被肝素、硫酸肝素或抗肽F-9抗体阻断。结合分析表明，F-9与HSPG相互作用，但不与LM或IV型胶原相互作用。胚肺细胞与多肽F-9预孵育后，细胞对HSPG的黏附显著增加，但对其他主要BM成分的黏附作用不明显。这些发现表明，Lm和BM HSPG之间的相互作用在上皮细胞极化和管腔形成的发展中起关键作用。这种相互作用发生在上皮-间充质交界处，并由以多肽F-9和HSPG的硫酸乙酰肝素基团为代表的LM分子中的一个位点介导。
The extracellular matrix and in particular the basement membrane (BM) play an important role in the induction of organotypic rearrangement of cells in culture. This process involves cell aggregation, sorting into epithelial and mesenchymal components, epithelial cell polarization, and lumen formation. In this study, a combination of laminin (LM) and heparan sulfate proteoglycan (HSPG), two major BM constituents, induced organotypic rearrangement of embryonic mouse lung cells. In the absence of LM/HSPG supplementation, the cells sorted into epithelial and mesenchymal compartments but epithelial cell polarization and lumen formation did not occur. Neither LM nor HSPG alone could trigger this process. Synthetic peptide F-9, representing an amino acid sequence from the inner globular region of the laminin β1 chain (RYVVLPRPVCFEKGMNYTVR) induced organotypic cell rearrangement when substituted for LM. Exogenous LM as well as peptide F-9 were localized at the epithelial–mesenchymal interface of organotypic cultures, where a BM-like structure is formedde novo.Organotypic cell rearrangement was blocked by heparin, heparan sulfate, or antibodies against peptide F-9. Binding assays indicated that peptide F-9 interacts with HSPG but not with LM or type IV collagen. Preincubation of embryonic lung cells with peptide F-9 resulted in a significant increase in cell attachment to HSPG but not to other major BM constituents. These findings suggest that the interaction between LM and BM HSPG is critical for the development of epithelial cell polarization and lumen formation. This interaction occurs at the epithelial–mesenchymal interface and is mediated by a site in the LM molecule represented by peptide F-9 and the heparan sulfate groups of HSPG.