Inhibition of precardiac mesoderm cell proliferation by antisense oligodeoxynucleotide complementary to fibroblast growth factor-2 (FGF-2). Dev Biol 1993 May;157(1):28-37
Date
05/01/1993Pubmed ID
8482417DOI
10.1006/dbio.1993.1109Scopus ID
2-s2.0-0027238422 (requires institutional sign-in at Scopus site) 85 CitationsAbstract
This laboratory recently reported the occurrence of concentrated deposits of fibroblast growth factor-2 (FGF-2; basic FGF)-like proteins in the sarcoplasm of embryonic cardiac myocytes from the earliest stage of avian heart development (M. H. Parlow, D. L. Bolender, N. P. Kokan-Moore, and J. Lough, Dev. Biol. 146, 139, 1991). To determine the role, if any, of FGF-2 during embryonic cardiogenesis, the proliferative and functional effects of treating cultured anterior lateral plate mesoderm from Hamburger-Hamilton stage 6 embryos with antisense oligodeoxynucleotide (ODN) complementary to FGF-2 mRNA were determined. Within 2 days of culture in defined medium, the explanted monolayer normally differentiates into a multilayer of proliferative cells that express sarcomeric alpha-actin and exhibit rhythmic contractions. The inclusion of 25 microM ODN that is complementary to the second exon of chicken FGF-2 mRNA caused a 50% inhibition in these cells' proliferative ability as judged by incorporation of 5'-bromodeoxyuridine; contractility was similarly inhibited. These effects were prevented by including recombinant human FGF-2 protein in the medium. Treatment with sense ODN did not cause inhibition. Inhibition of FGF-2 protein synthesis in the explanted tissue by antisense ODN was verified by immunoprecipitation analysis. These results point to a critical role for FGF-2 in the autocrine regulation of proliferation, and perhaps differentiative function, of embryonic cardiac myocytes.
Author List
Sugi Y, Sasse J, Lough JAuthor
John W. Lough PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAnimals
Antibodies
Base Sequence
Cell Division
Chick Embryo
Chickens
Exons
Fibroblast Growth Factor 2
Heart
Mesoderm
Molecular Sequence Data
Myocardial Contraction
Oligonucleotides, Antisense
Organ Culture Techniques
Peptides
Polymerase Chain Reaction
RNA, Messenger