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PMID: 2504143 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Collagen synthesis by human fibroblasts. Regulation by transforming growth factor-beta in the presence of other inflammatory mediators.

The Biochemical journal ·Vol. 260 ·No. 2 ·1989-06-01 ·Pages 463-9

Narayanan AS, Page RC, Swanson J

Abstract

We have examined the combined effects of transforming growth factor-beta (TGF-beta), serum and gamma-interferon (gamma-IFN) on collagen synthesis by fibroblasts and compared the response of fibroblast subpopulations to TGF-beta. Human diploid fibroblasts were treated with TGF-beta alone and with serum of gamma-IFN. Cells were labelled with radioactive amino acids, and collagen production was measured as collagenase-digestible radioactivity. Collagen mRNA was determined by a solution-hybridization assay using procollagen-alpha 1[I] cDNA clone HF 677. The results showed that either serum or TGF-beta increased incorporation, collagen production and mRNA by fibroblasts approx. 2-fold; however, collagen synthesis relative to total protein synthesis and collagen mRNA relative to total polyadenylated [poly(A)+] RNA were not affected. Only serum activated cell growth. Collagen production increased approx. 4-fold in cells exposed to both TGF-beta and serum, and this increase was equal to that expected for an additive effect by both components. Treatment with gamma-IFN decreased collagen production and collagen mRNA to 44 and 40% respectively, whereas total incorporation and poly(A)+ RNA were affected only marginally. Cells exposed simultaneously to both gamma-IFN and TGF-beta produced less collagen and contained less mRNA than did those treated with TGF-beta alone. The gamma-IFN decreased collagen synthesis in control and TGF-beta-treated cultures to a similar extent, and TGF-beta increased collagen synthesis 2-fold in cells pre-treated with gamma-IFN. Fibroblast strains obtained in medium containing plasma-derived serum synthesized approximately half as much collagen as did cells derived from the same explant in the presence of fresh human serum, and TGF-beta stimulated collagen production and mRNA in both cell strains. We conclude that TGF-beta, serum and gamma-IFN regulate collagen synthesis by independent mechanisms, and that the combined action of these components plays a significant role in regulating collagen synthesis during wound healing and tissue repair.

MeSH Terms
Cells, Cultured Collagen/biosynthesis Fibroblasts/drug effects,metabolism Humans Interferon-gamma/pharmacology Recombinant Proteins Transforming Growth Factors/pharmacology
Chemicals
Recombinant Proteins Transforming Growth Factors Interferon-gamma Collagen
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Narayanan A S
Department of Pathology, University of Washington, Seattle 98195.
Page R C
Swanson J
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/bj2600463
Published
1989-06-01
Pages
463-9
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1138691
Subset
IM
Grants
NIDCR NIH HHS · DE-02600 · United States
NIDCR NIH HHS · DE-03301 · United States
External Links
PubMed source DOI: 10.1042/bj2600463 PMC Full Text View journal details
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