Amano Tosikazu, Fu Liezhen, Marshak Anastasia, Kwak Olivia, Shi Yun-Bo
Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Dev Dyn. 2005 Sep;234(1):190-200. doi: 10.1002/dvdy.20511.
The 37-kd laminin receptor precursor (LR) was first identified as a 67-kd protein that binds laminin with high affinity. We have recently isolated the Xenopus laevis LR as an in vitro substrate of matrix metalloproteinase stromelysin-3 (ST3), which is highly upregulated during intestinal metamorphosis in Xenopus laevis. Here, we show that LR is expressed in the intestinal epithelium of premetamorphic tadpoles. During intestinal metamorphosis, LR is downregulated in the apoptotic epithelium and concurrently upregulated in the connective tissue but with little expression in the developing adult epithelium. Toward the end of metamorphosis, as adult epithelial cells differentiate, they begin to express LR. Furthermore, LR is cleaved during intestinal remodeling when ST3 is highly expressed or in premetamorphic intestine of transgenic tadpoles overexpressing ST3. These results suggest that LR plays a role in cell fate determination and tissue morphogenesis, in part through its cleavage by ST3. Interestingly, high levels of LR are known to be expressed in tumor cells, which are often surrounded by fibroblasts expressing ST3, suggesting that LR cleavage by ST3 plays a role in both physiological and pathological processes.
37-kD层粘连蛋白受体前体（LR）最初被鉴定为一种能与层粘连蛋白高亲和力结合的67-kD蛋白。我们最近分离出非洲爪蟾的LR，它是基质金属蛋白酶基质溶素-3（ST3）的体外底物，在非洲爪蟾肠道变态过程中ST3高度上调。在此，我们表明LR在前变态期蝌蚪的肠上皮中表达。在肠道变态过程中，LR在凋亡上皮中下调，同时在结缔组织中上调，但在发育中的成体上皮中表达很少。在变态末期，随着成体上皮细胞分化，它们开始表达LR。此外，当ST3高度表达时，或在过表达ST3的转基因蝌蚪的前变态期肠道中，LR在肠道重塑过程中被切割。这些结果表明，LR在细胞命运决定和组织形态发生中发挥作用，部分是通过其被ST3切割实现的。有趣的是，已知肿瘤细胞中高水平表达LR，而肿瘤细胞周围通常有成纤维细胞表达ST3，这表明ST3切割LR在生理和病理过程中都起作用。
