Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming, Yunnan, China.
Cell Mol Life Sci. 2011 Nov;68(22):3771-80. doi: 10.1007/s00018-011-0678-6. Epub 2011 Apr 3.
Trefoil factors (TFFs) promote epithelial cell migration to reseal superficial wounds after mucosal injury, but their receptors and the molecular mechanisms underlying this process are poorly understood. In this study, we showed that frog TFF2 activates protease-activated receptor (PAR) 1 to induce human platelet aggregation. Based on this result, we further tested the involvement of PARs in human TFF2 (hTFF2)-promoted mucosal healing. hTFF2-stimulated migration of epithelial HT-29 cells was largely inhibited by PAR4 depletion with small interfering RNAs but not by PAR1 or PAR2 depletion. The PAR4-negative epithelial cell lines AGS and LoVo were highly responsive to hTFF2 as assessed by phosphorylation of ERK1/2 and cell migration upon PAR4 expression. Our findings suggest that hTFF2 promotes cell migration via PAR4. These findings will be helpful in further investigations into the functions and molecular mechanisms of TFFs and PARs in physiology and disease.
三叶因子（TFFs）促进上皮细胞迁移以重新封闭黏膜损伤后的浅表伤口，但它们的受体以及该过程的分子机制尚不清楚。在这项研究中，我们表明蛙 TFF2 激活蛋白酶激活受体（PAR）1 以诱导人血小板聚集。基于这一结果，我们进一步测试了 PAR 在人 TFF2（hTFF2）促进黏膜愈合中的参与。用小干扰 RNA 耗竭 PAR4 可显著抑制 hTFF2 刺激的上皮 HT-29 细胞迁移，但用 PAR1 或 PAR2 耗竭则不能。PAR4 阴性上皮细胞系 AGS 和 LoVo 在 PAR4 表达后通过 ERK1/2 磷酸化和细胞迁移对 hTFF2 高度反应。我们的发现表明 hTFF2 通过 PAR4 促进细胞迁移。这些发现将有助于进一步研究 TFF 和 PAR 在生理和疾病中的功能和分子机制。
