• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. Sep 15, 1998; 102(6): 1208–1219.
PMCID: PMC509104

An endothelial growth factor involved in rat renal development.

Abstract

In the kidney, there is a close and intricate association between epithelial and endothelial cells, suggesting that a complex reciprocal interaction may exist between these two cell types during renal ontogeny. Thus, we examined whether metanephrogenic mesenchymal cells secrete endothelial mitogens. With an endothelial mitogenic assay and sequential chromatography of the proteins in the media conditioned by a cell line of rat metanephrogenic mesenchymal cells (7.1.1 cells), we isolated a protein whose amino acid analysis identified it as hepatoma-derived growth factor (HDGF). Media conditioned with Cos-7 cell transfected with HDGF cDNA stimulated endothelial DNA synthesis. With immunoaffinity purified antipeptide antibodies, we found that HDGF was widely distributed in the renal anlage at early stages of development but soon concentrated at sites of active morphogenesis and, except for some renal tubules, disappeared from the adult kidney. From a 7.1.1 cells cDNA library, a clone of most of the translatable region of HDGF was obtained and used to synthesize digoxigenin-labeled riboprobes. In situ hybridization showed that during kidney development mRNA for HDGF was most abundant at sites of nephron morphogenesis and in ureteric bud cells while in the adult kidney transcripts disappeared except for a small population of distal tubules. Thus, HDGF is an endothelial mitogen that is present in embryonic kidney, and its expression is synchronous with nephrogenesis.

Full Text

The Full Text of this article is available as a PDF (1.0M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Oliver JA, Goldberg MR, Al-Awqati Q. Endothelial cell targeting during renal development: use of monoclonal antibodies. Am J Physiol. 1997 Feb;272(2 Pt 2):F153–F159. [PubMed]
  • Oelrichs RB, Reid HH, Bernard O, Ziemiecki A, Wilks AF. NYK/FLK-1: a putative receptor protein tyrosine kinase isolated from E10 embryonic neuroepithelium is expressed in endothelial cells of the developing embryo. Oncogene. 1993 Jan;8(1):11–18. [PubMed]
  • Simon M, Gröne HJ, Jöhren O, Kullmer J, Plate KH, Risau W, Fuchs E. Expression of vascular endothelial growth factor and its receptors in human renal ontogenesis and in adult kidney. Am J Physiol. 1995 Feb;268(2 Pt 2):F240–F250. [PubMed]
  • Breier G, Albrecht U, Sterrer S, Risau W. Expression of vascular endothelial growth factor during embryonic angiogenesis and endothelial cell differentiation. Development. 1992 Feb;114(2):521–532. [PubMed]
  • Monacci WT, Merrill MJ, Oldfield EH. Expression of vascular permeability factor/vascular endothelial growth factor in normal rat tissues. Am J Physiol. 1993 Apr;264(4 Pt 1):C995–1002. [PubMed]
  • Sariola H, Ekblom P, Lehtonen E, Saxén L. Differentiation and vascularization of the metanephric kidney grafted on the chorioallantoic membrane. Dev Biol. 1983 Apr;96(2):427–435. [PubMed]
  • Nakamura H, Izumoto Y, Kambe H, Kuroda T, Mori T, Kawamura K, Yamamoto H, Kishimoto T. Molecular cloning of complementary DNA for a novel human hepatoma-derived growth factor. Its homology with high mobility group-1 protein. J Biol Chem. 1994 Oct 7;269(40):25143–25149. [PubMed]
  • McGuire PG, Orkin RW. Isolation of rat aortic endothelial cells by primary explant techniques and their phenotypic modulation by defined substrata. Lab Invest. 1987 Jul;57(1):94–105. [PubMed]
  • HUNTER WM, GREENWOOD FC. Preparation of iodine-131 labelled human growth hormone of high specific activity. Nature. 1962 May 5;194:495–496. [PubMed]
  • Oliver JA. Purification and partial characterization of canine angiotensinogen. Hypertension. 1988 Jan;11(1):21–27. [PubMed]
  • Alpers CE, Seifert RA, Hudkins KL, Johnson RJ, Bowen-Pope DF. Developmental patterns of PDGF B-chain, PDGF-receptor, and alpha-actin expression in human glomerulogenesis. Kidney Int. 1992 Aug;42(2):390–399. [PubMed]
  • Parkkinen J, Raulo E, Merenmies J, Nolo R, Kajander EO, Baumann M, Rauvala H. Amphoterin, the 30-kDa protein in a family of HMG1-type polypeptides. Enhanced expression in transformed cells, leading edge localization, and interactions with plasminogen activation. J Biol Chem. 1993 Sep 15;268(26):19726–19738. [PubMed]
  • Rauvala H, Pihlaskari R. Isolation and some characteristics of an adhesive factor of brain that enhances neurite outgrowth in central neurons. J Biol Chem. 1987 Dec 5;262(34):16625–16635. [PubMed]
  • Hori O, Brett J, Slattery T, Cao R, Zhang J, Chen JX, Nagashima M, Lundh ER, Vijay S, Nitecki D, et al. The receptor for advanced glycation end products (RAGE) is a cellular binding site for amphoterin. Mediation of neurite outgrowth and co-expression of rage and amphoterin in the developing nervous system. J Biol Chem. 1995 Oct 27;270(43):25752–25761. [PubMed]
  • Rauvala H, Merenmies J, Pihlaskari R, Korkolainen M, Huhtala ML, Panula P. The adhesive and neurite-promoting molecule p30: analysis of the amino-terminal sequence and production of antipeptide antibodies that detect p30 at the surface of neuroblastoma cells and of brain neurons. J Cell Biol. 1988 Dec;107(6 Pt 1):2293–2305. [PMC free article] [PubMed]
  • Merenmies J, Pihlaskari R, Laitinen J, Wartiovaara J, Rauvala H. 30-kDa heparin-binding protein of brain (amphoterin) involved in neurite outgrowth. Amino acid sequence and localization in the filopodia of the advancing plasma membrane. J Biol Chem. 1991 Sep 5;266(25):16722–16729. [PubMed]
  • Neeper M, Schmidt AM, Brett J, Yan SD, Wang F, Pan YC, Elliston K, Stern D, Shaw A. Cloning and expression of a cell surface receptor for advanced glycosylation end products of proteins. J Biol Chem. 1992 Jul 25;267(21):14998–15004. [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...