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. 1991 Apr;138(4):1035–1043.

Hepatocyte growth factor in human placenta and trophoblastic disease.

H K Wolf 1, R Zarnegar 1, L Oliver 1, G K Michalopoulos 1
PMCID: PMC1886112  PMID: 1849357

Abstract

The hepatocyte growth factor (HGF) is an acidic protein with a strong mitogenic effect on hepatocytes. Hepatocyte growth factor mRNA recently was cloned from a placental cDNA library. Here we demonstrate the purification of HGF from human placenta with heparin-agarose chromatography and TSK-heparin high-pressure liquid chromatography and describe the distribution of placental HGF by immunohistochemistry using a polyclonal antibody to HGF. The yield of HGF from the placenta was approximately 100 to 200 times greater than that previously obtained from human plasma. Placental HGF was expressed strongly in the villous syncytium, extravillous trophoblast, and amnionic epithelium, and, to a lesser degree in endothelial cells and villous mesenchyme. Hepatocyte growth factor also was identified in the trophoblast of complete hydatidiform moles, choriocarcinomas, and a case of blighted ovum. The presence of HGF in an organ characterized by rapid cell proliferation during gestation and in trophoblastic tumors strongly suggests that the growth-regulating effect of HGF is not limited to hepatocytes.

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Selected References

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  1. Adamson E. D. Extraembryonic tissues as sources and sinks of humoral factors in development: teratocarcinoma model systems. Prog Clin Biol Res. 1986;226:159–174. [PubMed] [Google Scholar]
  2. Al-Timimi A., Fox H. Immunohistochemical localization of follicle-stimulating hormone, luteinizing hormone, growth hormone, adrenocorticotrophic hormone and prolactin in the human placenta. Placenta. 1986 Mar-Apr;7(2):163–172. doi: 10.1016/s0143-4004(86)80007-8. [DOI] [PubMed] [Google Scholar]
  3. Albrecht E. D., Pepe G. J. Placental steroid hormone biosynthesis in primate pregnancy. Endocr Rev. 1990 Feb;11(1):124–150. doi: 10.1210/edrv-11-1-124. [DOI] [PubMed] [Google Scholar]
  4. Boehm K. D., Kelley M. F., Ilan J., Ilan J. The interleukin 2 gene is expressed in the syncytiotrophoblast of the human placenta. Proc Natl Acad Sci U S A. 1989 Jan;86(2):656–660. doi: 10.1073/pnas.86.2.656. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gohda E., Tsubouchi H., Nakayama H., Hirono S., Sakiyama O., Takahashi K., Miyazaki H., Hashimoto S., Daikuhara Y. Purification and partial characterization of hepatocyte growth factor from plasma of a patient with fulminant hepatic failure. J Clin Invest. 1988 Feb;81(2):414–419. doi: 10.1172/JCI113334. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kurman R. J., Main C. S., Chen H. C. Intermediate trophoblast: a distinctive form of trophoblast with specific morphological, biochemical and functional features. Placenta. 1984 Jul-Aug;5(4):349–369. doi: 10.1016/s0143-4004(84)80015-6. [DOI] [PubMed] [Google Scholar]
  7. Kurman R. J., Young R. H., Norris H. J., Main C. S., Lawrence W. D., Scully R. E. Immunocytochemical localization of placental lactogen and chorionic gonadotropin in the normal placenta and trophoblastic tumors, with emphasis on intermediate trophoblast and the placental site trophoblastic tumor. Int J Gynecol Pathol. 1984;3(1):101–121. doi: 10.1097/00004347-198403010-00009. [DOI] [PubMed] [Google Scholar]
  8. Laatikainen T., Saijonmaa O., Salminen K., Wahlström T. Localization and concentrations of beta-endorphin and beta-lipotrophin in human placenta. Placenta. 1987 Jul-Aug;8(4):381–387. doi: 10.1016/0143-4004(87)90065-8. [DOI] [PubMed] [Google Scholar]
  9. MIDGLEY A. R., Jr, PIERCE G. B., Jr Immunohistochemical localization of human chorionic gonadotropin. J Exp Med. 1962 Feb 1;115:289–294. doi: 10.1084/jem.115.2.289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Michalopoulos G. K. Liver regeneration: molecular mechanisms of growth control. FASEB J. 1990 Feb 1;4(2):176–187. [PubMed] [Google Scholar]
  11. Miyazawa K., Tsubouchi H., Naka D., Takahashi K., Okigaki M., Arakaki N., Nakayama H., Hirono S., Sakiyama O., Takahashi K. Molecular cloning and sequence analysis of cDNA for human hepatocyte growth factor. Biochem Biophys Res Commun. 1989 Sep 15;163(2):967–973. doi: 10.1016/0006-291x(89)92316-4. [DOI] [PubMed] [Google Scholar]
  12. Nakamura T., Nawa K., Ichihara A., Kaise N., Nishino T. Purification and subunit structure of hepatocyte growth factor from rat platelets. FEBS Lett. 1987 Nov 30;224(2):311–316. doi: 10.1016/0014-5793(87)80475-1. [DOI] [PubMed] [Google Scholar]
  13. Nakamura T., Nishizawa T., Hagiya M., Seki T., Shimonishi M., Sugimura A., Tashiro K., Shimizu S. Molecular cloning and expression of human hepatocyte growth factor. Nature. 1989 Nov 23;342(6248):440–443. doi: 10.1038/342440a0. [DOI] [PubMed] [Google Scholar]
  14. Saijonmaa O., Laatikainen T., Wahlström T. Corticotrophin-releasing factor in human placenta: localization, concentration and release in vitro. Placenta. 1988 Jul-Aug;9(4):373–385. doi: 10.1016/0143-4004(88)90050-1. [DOI] [PubMed] [Google Scholar]
  15. Sakbun V., Ali S. M., Lee Y. A., Jara C. S., Bryant-Greenwood G. D. Immunocytochemical localization and messenger ribonucleic acid concentrations for human placental lactogen in amnion, chorion, decidua, and placenta. Am J Obstet Gynecol. 1990 May;162(5):1310–1317. doi: 10.1016/0002-9378(90)90043-7. [DOI] [PubMed] [Google Scholar]
  16. Sasagawa M., Yamazaki T., Endo M., Kanazawa K., Takeuchi S. Immunohistochemical localization of HLA antigens and placental proteins (alpha hCG, beta hCG CTP, hPL and SP1 in villous and extravillous trophoblast in normal human pregnancy: a distinctive pathway of differentiation of extravillous trophoblast. Placenta. 1987 Sep-Oct;8(5):515–528. doi: 10.1016/0143-4004(87)90080-4. [DOI] [PubMed] [Google Scholar]
  17. Selden C., Johnstone R., Darby H., Gupta S., Hodgson H. J. Human serum does contain a high molecular weight hepatocyte growth factor: studies pre- and post-hepatic resection. Biochem Biophys Res Commun. 1986 Aug 29;139(1):361–366. doi: 10.1016/s0006-291x(86)80122-x. [DOI] [PubMed] [Google Scholar]
  18. Selden C., Jones M., Wade D., Hodgson H. Hepatotropin mRNA expression in human foetal liver development and in liver regeneration. FEBS Lett. 1990 Sep 17;270(1-2):81–84. doi: 10.1016/0014-5793(90)81239-k. [DOI] [PubMed] [Google Scholar]
  19. Tashiro K., Hagiya M., Nishizawa T., Seki T., Shimonishi M., Shimizu S., Nakamura T. Deduced primary structure of rat hepatocyte growth factor and expression of the mRNA in rat tissues. Proc Natl Acad Sci U S A. 1990 Apr;87(8):3200–3204. doi: 10.1073/pnas.87.8.3200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. WISLOCKI G. B., FAWCETT D. W., DEMPSEY E. W. Staining of stratified squamous epithelium of mucous membranes and skin of man and monkey by the periodic acid-Schiff method. Anat Rec. 1951 Jul;110(3):359–375. doi: 10.1002/ar.1091100307. [DOI] [PubMed] [Google Scholar]
  21. Wang C. Y., Daimon M., Shen S. J., Engelmann G. L., Ilan J. Insulin-like growth factor-I messenger ribonucleic acid in the developing human placenta and in term placenta of diabetics. Mol Endocrinol. 1988 Mar;2(3):217–229. doi: 10.1210/mend-2-3-217. [DOI] [PubMed] [Google Scholar]
  22. Zarnegar R., Michalopoulos G. Purification and biological characterization of human hepatopoietin A, a polypeptide growth factor for hepatocytes. Cancer Res. 1989 Jun 15;49(12):3314–3320. [PubMed] [Google Scholar]
  23. Zarnegar R., Muga S., Rahija R., Michalopoulos G. Tissue distribution of hepatopoietin-A: a heparin-binding polypeptide growth factor for hepatocytes. Proc Natl Acad Sci U S A. 1990 Feb;87(3):1252–1256. doi: 10.1073/pnas.87.3.1252. [DOI] [PMC free article] [PubMed] [Google Scholar]

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