Zhang Jianhu, Li Wei, Sanders Matthew A, Sumpio Bauer E, Panja Asit, Basson Marc D
Departments of Surgery, Wayne State University, USA.
FASEB J. 2003 May;17(8):926-8. doi: 10.1096/fj.02-0663fje. Epub 2003 Mar 5.
Repetitive mechanical deformation may stimulate intestinal epithelial proliferation. Because the extracellular matrix modulates static intestinal epithelial biology, we examined whether matrix proteins influence intestinal epithelial responses to deformation. Human Caco-2BBE cells and nontransformed human enterocytes (HIPEC) were subjected to 10% average cyclic strain at 10 cycles/min on flexible membranes precoated with matrix proteins without or with plasma fibronectin or functional anti-integrin antibodies in the medium. Strain stimulated proliferation, focal adhesion kinase, extracellular signal-regulated protein kinase (ERK), p38, and Jun N-terminal kinase similarly on collagen I or IV, and more weakly on laminin, but had no effect on fibronectin. MEK blockade (PD98059) prevented strain-stimulated proliferation on collagen but did not affect proliferation on fibronectin. Adding tissue fibronectin to a collagen substrate or plasma fibronectin to the media suppressed strain s mitogenic and signal effects, but not those of epidermal growth factor. Functional antibodies to the alpha5 or alpha(v) integrin subunit blocked strain's effects on Caco-2 proliferation and ERK activation, although ligation of the alpha2 or alpha6 subunit did not. Repetitive strain also stimulated, and fibronectin inhibited, human intestinal primary epithelial cell proliferation. Repetitive deformation stimulates transformed and nontransformed human intestinal epithelial proliferation in a matrix-dependent manner. Tissue or plasma fibronectin may regulate the intestinal epithelial response to strain via integrins containing alpha5 or alpha(v).
重复性机械变形可能会刺激肠上皮细胞增殖。由于细胞外基质调节静止状态下的肠上皮生物学特性，我们研究了基质蛋白是否会影响肠上皮细胞对变形的反应。将人Caco-2BBE细胞和未转化的人肠上皮细胞（HIPEC）置于预涂有基质蛋白的柔性膜上，在培养基中添加或不添加血浆纤连蛋白或功能性抗整合素抗体的情况下，以10次/分钟的频率施加10%的平均循环应变。应变在I型或IV型胶原上对增殖、粘着斑激酶、细胞外信号调节蛋白激酶（ERK）、p38和c-Jun氨基末端激酶的刺激作用相似，在层粘连蛋白上的刺激作用较弱，但对纤连蛋白无影响。MEK阻断剂（PD98059）可阻止应变在胶原上刺激的增殖，但不影响在纤连蛋白上的增殖。向胶原底物中添加组织纤连蛋白或向培养基中添加血浆纤连蛋白可抑制应变的促有丝分裂和信号作用，但不影响表皮生长因子的作用。针对α5或α(v)整合素亚基的功能性抗体可阻断应变对Caco-2增殖和ERK激活的作用，而针对α2或α6亚基的连接则无此作用。重复性应变也刺激了人肠道原代上皮细胞的增殖，而纤连蛋白则抑制了这种增殖。重复性变形以基质依赖的方式刺激转化和未转化的人肠上皮细胞增殖。组织或血浆纤连蛋白可能通过含有α5或α(v)的整合素来调节肠上皮细胞对应变的反应。
