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Am J Physiol Gastrointest Liver Physiol. 2010 Jun;298(6):G994-G1003. doi: 10.1152/ajpgi.00517.2009. Epub 2010 Mar 18.
The intestinal epithelium is subjected to repetitive deformation during normal gut function by peristalsis and villous motility. In vitro, cyclic strain promotes intestinal epithelial proliferation and induces an absorptive phenotype characterized by increased dipeptidyl dipeptidase (DPPIV) expression. Schlafen 3 is a novel gene recently associated with cellular differentiation. We sought to evaluate whether Schlafen 3 mediates the effects of strain on the differentiation of intestinal epithelial cell (IEC)-6 in the absence or presence of cyclic strain. Strain increased Schlafen 3 mRNA and protein. In cells transfected with a control-nontargeting siRNA, strain increased DPPIV-specific activity. However, Schlafen 3 reduction by siRNA decreased basal DPPIV and prevented any stimulation of DPPIV activity by strain. Schlafen 3 reduction also prevented DPPIV induction by sodium butyrate (1 mM) or transforming growth factor (TGF)-beta (0.1 ng/ml), two unrelated differentiating stimuli. However, Schlafen-3 reduction by siRNA did not prevent the mitogenic effect of strain or that of EGF. Blocking Src and phosphatidyl inositol (PI3)-kinase prevented strain induction of Schlafen 3, but Schlafen 3 induction required activation of p38 but not ERK. These results suggest that cyclic strain induces an absorptive phenotype characterized by increased DPPIV activity via Src-, p38-, and PI3-kinase-dependent induction of Schlafen 3 in rat IEC-6 cells on collagen, whereas Schlafen 3 may also be a key factor in the induction of intestinal epithelial differentiation by other stimuli such as sodium butyrate or TGF-beta. The induction of Schlafen 3 or its human homologs may modulate intestinal epithelial differentiation and preserve the gut mucosa during normal gut function.
肠上皮在正常肠道功能中通过蠕动和绒毛运动反复受到变形。在体外，周期性张力促进肠上皮细胞增殖，并诱导具有增加的二肽基肽酶（DPPIV）表达的吸收表型。 Schlafen 3 是最近与细胞分化相关的新基因。我们试图评估 Schlafen 3 是否介导张力对肠上皮细胞（IEC）-6分化的影响，无论是否存在周期性张力。张力增加 Schlafen 3 mRNA 和蛋白。在转染对照非靶向 siRNA 的细胞中，张力增加 DPPIV 特异性活性。然而，siRNA 减少 Schlafen 3 降低了基础 DPPIV 并阻止了张力对 DPPIV 活性的任何刺激。 Schlafen 3 减少也阻止了 DPPIV 由丁酸钠（1 mM）或转化生长因子（TGF）-β（0.1 ng/ml）诱导，这两种无关的分化刺激物。然而，siRNA 减少 Schlafen-3 并没有阻止张力或 EGF 的有丝分裂作用。阻断Src 和磷脂酰肌醇（PI3）-激酶可防止张力诱导 Schlafen 3，但 Schlafen 3 诱导需要 p38 但不需要 ERK 的激活。这些结果表明，周期性张力通过 Src-、p38-和 PI3-激酶依赖性诱导大鼠 IEC-6 细胞在胶原蛋白上的 Schlafen 3，从而诱导吸收表型，其特征是 DPPIV 活性增加，而 Schlafen 3 也可能是其他刺激物（如丁酸钠或 TGF-β）诱导肠上皮细胞分化的关键因素。 Schlafen 3 或其人类同源物的诱导可能调节肠上皮细胞分化并在正常肠道功能期间保护肠道黏膜。
