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PMID: 2447102 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Regulation of human mesothelial cell differentiation: opposing roles of retinoids and epidermal growth factor in the expression of intermediate filament proteins.

The Journal of cell biology ·Vol. 105 ·No. 6 Pt 2 ·1987-12-00 ·Pages 3039-51

Kim KH, Stellmach V, Javors J, Fuchs E

Abstract

We report here the discovery that retinoids are potent regulators of epithelial morphology and keratin expression in cultured human mesothelial cells. When LP-9 cells are cultured in medium supplemented with vitamin A-depleted serum, they grow with an extreme spindle-shaped morphology and synthesize abundant levels of vimentin, but very little keratin. When retinoic acid is added to the medium at 1 X 10(-8) to 1 X 10(-6) M, keratin synthesis is increased, vimentin synthesis is decreased, and the cells assume an epithelioid morphology. Keratin synthesis, but not epithelioid morphology, seems to be dependent on cell density as well: even when vitamin A is present, sparse cultures cannot fully maintain keratin synthesis. In contrast, epidermal growth factor (EGF) acts in an antagonistic fashion to suppress both keratin synthesis and epithelial morphology. The effects of vitamin A, EGF, and cell shape on intermediate filament (IF) expression seem to occur in a growth-independent manner, and they appear to be at the level of transcription or mRNA stability. Even so, their effects on IF expression do not appear to be rapid ones, and hence it is unlikely that these agents interact directly at the gene level to cause changes in IF gene expression.

MeSH Terms
Actins/genetics Cell Differentiation/drug effects Culture Media Cytoskeleton/physiology Epidermal Growth Factor/pharmacology Epithelial Cells Gene Expression Regulation/drug effects Humans Intermediate Filaments/physiology Isoelectric Point Keratins/genetics Kinetics Molecular Weight RNA, Messenger/genetics Tubulin/metabolism Tumor Cells, Cultured Vimentin/genetics Vitamin A/pharmacology
Chemicals
Actins Culture Media RNA, Messenger Tubulin Vimentin Vitamin A Epidermal Growth Factor Keratins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kim K H
Department of Molecular Genetics and Cell Biology, University of Chicago, Illinois 60637.
Stellmach V
Javors J
Fuchs E
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.105.6.3039
Published
1987-12-00
Pages
3039-51
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2114710
Subset
IM
Grants
NIAMS NIH HHS · AR-31737 · United States
External Links
PubMed source DOI: 10.1083/jcb.105.6.3039 PMC Full Text View journal details
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