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PMID: 2586525 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Complex regulation of transforming growth factor beta 1, beta 2, and beta 3 mRNA expression in mouse fibroblasts and keratinocytes by transforming growth factors beta 1 and beta 2.

Molecular and cellular biology ·Vol. 9 ·No. 12 ·1989-12-00 ·Pages 5508-15

Bascom CC, Wolfshohl JR, Coffey RJ, Madisen L, Webb NR, Purchio AR, Derynck R, Moses HL

Abstract

Regulation of transforming growth factor beta 1 (TGF beta 1), TGF beta 2, and TGF beta 3 mRNAs in murine fibroblasts and keratinocytes by TGF beta 1 and TGF beta 2 was studied. In quiescent AKR-2B fibroblasts, in which TGF beta induces delayed stimulation of DNA synthesis, TGF beta 1 autoregulation of TGF beta 1 expression was observed as early as 1 h, with maximal induction (25-fold) after 6 to 12 h. Increased expression of TGF beta 1 mRNA was accompanied by increased TGF beta protein production into conditioned medium of AKR-2B cells. Neither TGF beta 2 nor TGF beta 3 mRNA, however, was significantly induced, but both were apparently down regulated at later times by TGF beta 1. Protein synthesis was not required for autoinduction of TGF beta 1 mRNA in AKR-2B cells. Nuclear run-on analyses and dactinomycin experiments indicated that autoregulation of TGF beta 1 expression is complex, involving both increased transcription and message stabilization. In contrast to TGF beta 1, TGF beta 2 treatment of quiescent AKR-2B cells increased expression of TGF beta 1, TGF beta 2, and TGF beta 3 mRNAs, but with different kinetics. Autoinduction of TGF beta 2 mRNA occurred rapidly with maximal induction at 1 to 3 h, enhanced TGF beta 3 mRNA levels were observed after 3 h, and increased expression of TGF beta 1 occurred later, with maximal mRNA levels obtained after 12 to 24 h. Nuclear run-on analyses indicated that TGF beta 2 regulation of TGF beta 2 and TGF beta 3 mRNA levels is transcriptional, while TGF beta 2 induction of TGF beta 1 expression most likely involves both transcriptional and posttranscriptional controls. In BALB/MK mouse keratinocytes, minimal autoinduction of TGF beta 1 occurred at only the 12- and 24-h time points and protein synthesis was required for this autoinduction. The results of this study provide an example in which TGF beta 1 and TGF beta 2 elicit different responses and demonstrate that expression of TGF beta 1, and TGF beta 3 are regulated differently. The physiological relevance of TGF beta 1 autoinduction in the context of wound healing is discussed.

MeSH Terms
Animals Cell Nucleus/metabolism Cells, Cultured Cycloheximide/pharmacology Dactinomycin/pharmacology Fibroblasts/drug effects,metabolism Gene Expression Regulation/drug effects Genes/drug effects Keratinocytes/drug effects,metabolism Mice Mice, Inbred AKR Mice, Inbred BALB C RNA, Messenger/biosynthesis,drug effects,genetics Transcription, Genetic/drug effects Transforming Growth Factors/biosynthesis,genetics,pharmacology
Chemicals
RNA, Messenger Dactinomycin Transforming Growth Factors Cycloheximide
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Bascom C C
Department of Cell Biology, Vanderbilt University, Nashville, Tennessee 37232.
Wolfshohl J R
Coffey R J
Madisen L
Webb N R
Purchio A R
Derynck R
Moses H L
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.9.12.5508-5515.1989
Published
1989-12-00
Pages
5508-15
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC363721
Subset
IM
Grants
NCI NIH HHS · CA 09592 · United States
NCI NIH HHS · CA 42572 · United States
External Links
PubMed source DOI: 10.1128/mcb.9.12.5508-5515.1989 PMC Full Text View journal details
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