Fiorino A S, Zvibel I
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Cell Biol Int. 1996 Jul;20(7):489-99. doi: 10.1006/cbir.1996.0064.
We have investigated the effects of altered cell shape on the regulation of the 92 kDa type IV collagenase. In MDCK cells, anti-E-cadherin antibodies alter cell shape by disrupting normal cell-cell contacts, while sodium butyrate causes a marked flattening and spreading of cells. The disruption of cell-cell contacts led to a faint expression of the 92 kDa collagenase. This effect was enhanced by sodium butyrate, which by itself did not induce collagenase expression. In contrast, stromelysin expression was not regulated in these conditions. Although mRNA expression was enhanced, the secreted collagenase activity was not altered in these conditions in either cell line. Examination of cytoskeletal and extracellular matrix proteins and cell-cell and cell-matrix adhesion proteins by immunofluorescence and Western blot revealed a disruption of the actin network, tight junctions, and fibronectin deposition by anti E-cadherin antibodies, and alterations in actin, cytokeratin 8, cytokeratin 14, laminin and beta 1 integrin induced by sodium butyrate. Thus, the induction of collagenase expression in epithelial cells by disrupted cell-cell adhesion and sodium butyrate is associated with changes in cell shape and structure.
我们研究了细胞形状改变对92 kDa IV型胶原酶调节的影响。在MDCK细胞中，抗E-钙黏蛋白抗体通过破坏正常的细胞间接触来改变细胞形状，而丁酸钠会导致细胞明显变平并铺展。细胞间接触的破坏导致92 kDa胶原酶的微弱表达。丁酸钠增强了这种效应，其本身并不诱导胶原酶表达。相反，在这些条件下基质溶解素的表达不受调节。尽管mRNA表达增强，但在这两种细胞系的这些条件下，分泌的胶原酶活性均未改变。通过免疫荧光和蛋白质印迹法检测细胞骨架和细胞外基质蛋白以及细胞间和细胞-基质黏附蛋白，发现抗E-钙黏蛋白抗体破坏了肌动蛋白网络、紧密连接和纤连蛋白沉积，并且丁酸钠诱导了肌动蛋白、细胞角蛋白8、细胞角蛋白14、层粘连蛋白和β1整合素的改变。因此，细胞间黏附破坏和丁酸钠诱导上皮细胞中胶原酶表达与细胞形状和结构的变化有关。
