Montesano R, Matsumoto K, Nakamura T, Orci L
Department of Morphology, University Medical Center, Geneva, Switzerland.
Cell. 1991 Nov 29;67(5):901-8. doi: 10.1016/0092-8674(91)90363-4.
We have previously shown that Madin-Darby canine kidney (MDCK) epithelial cells grown in collagen gels in the presence of fibroblasts or fibroblast-conditioned medium (CM) form branching tubules, instead of the spherical cysts that develop under control conditions. We now report that the fibroblast-derived molecule responsible for epithelial tubulogenesis is hepatocyte growth factor (HGF). First, addition of exogenous HGF to cultures of MDCK cells induces formation of epithelial tubules. Second, the tubulogenic activity of fibroblast CM is completely abrogated by antibodies to HGF. These results demonstrate that HGF, a polypeptide that was identified as a mitogen for cultured hepatocytes, has the properties of a paracrine mediator of epithelial morphogenesis, and suggest that it may play important roles in the formation of parenchymal organs during embryonic development.
我们先前已经表明，在成纤维细胞或成纤维细胞条件培养基（CM）存在的情况下，在胶原凝胶中生长的Madin-Darby犬肾（MDCK）上皮细胞形成分支小管，而不是在对照条件下形成的球形囊肿。我们现在报告，负责上皮细胞形成小管的成纤维细胞衍生分子是肝细胞生长因子（HGF）。首先，向MDCK细胞培养物中添加外源性HGF可诱导上皮小管的形成。其次，针对HGF的抗体可完全消除成纤维细胞CM的小管形成活性。这些结果表明，HGF是一种被鉴定为培养肝细胞促有丝分裂原的多肽，具有上皮形态发生旁分泌介质的特性，并表明它可能在胚胎发育过程中实质器官的形成中发挥重要作用。
