Antagonistic effects of TGF-beta 1 and MSF on fibroblast migration and hyaluronic acid synthesis: Possible implications for dermal wound healing

I Ellis, A M Grey, A M Schor, S L Schor

Research output: Contribution to journalArticle

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Abstract

The migration of adult skin fibroblasts into three-dimensional collagen gel matrices is differentially affected by cell density, with subconfluent cells displaying a significantly elevated level of migration compared to confluent ones. Fetal fibroblasts differ from adult cells in that they display an elevated level of migration at both subconfluent and confluent cell densities. We have previously reported that this difference in behaviour results from the secretion by fetal fibroblasts of a 'migration stimulating factor' (MSF) which is not made by their normal adult counterparts, and that MSF appears to act by stimulating the synthesis of hyaluronic acid (HA). Data presented in this communication indicate that (a) MSF specifically stimulates the synthesis of high molecular weight species of HA, (b) TGF-beta 1 inhibits the elevated migration of adult fibroblasts plated at subconfluent cell density, (c) under these conditions, TGF-beta 1 induces a parallel decrease in the synthesis of high molecular weight HA and increase in the synthesis of low molecular weight HA, (d) TGF-beta 1 is a potent antagonist of MSF, effectively blocking its stimulation of cell migration and synthesis of high molecular weight HA, and (e) the inhibition of fibroblast migration by TGF-beta 1 does not appear to be a chemotactic response dependent upon the existence of a concentration gradient of the cytokine. Our observations regarding the inhibitory effects of TGF-beta 1 on fibroblast migration into 3D collagen gels stand in marked contrast to various published reports indicating that this cytokine stimulates the migration of human skin fibroblasts through the pores of polycarbonate filters as used in modified Boyden chamber assays; this discrepancy underscores the importance of the substratum in modulating cellular response to cytokines. Our results are discussed in terms of the possible combined contribution of MSF and TGF-beta 1 to wound healing.

Original languageEnglish
Pages (from-to)447-56
Number of pages10
JournalJournal of Cell Science
Volume102
Issue number3
Publication statusPublished - Jul 1992

Fingerprint

Transforming Growth Factor beta1
Hyaluronic Acid
Wound Healing
Fibroblasts
Skin
Molecular Weight
polycarbonate
Cell Count
Cytokines
Collagen
Gels
Cell Movement

Keywords

  • Cell Movement/physiology
  • Cells, Cultured
  • Child, Preschool
  • Collagen
  • Cytokines/physiology
  • Dose-Response Relationship, Drug
  • Fibroblasts/cytology
  • Fibronectins
  • Gels
  • Humans
  • Hyaluronic Acid/biosynthesis
  • Male
  • Transforming Growth Factor beta/physiology
  • Wound Healing/physiology

Cite this

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title = "Antagonistic effects of TGF-beta 1 and MSF on fibroblast migration and hyaluronic acid synthesis: Possible implications for dermal wound healing",
abstract = "The migration of adult skin fibroblasts into three-dimensional collagen gel matrices is differentially affected by cell density, with subconfluent cells displaying a significantly elevated level of migration compared to confluent ones. Fetal fibroblasts differ from adult cells in that they display an elevated level of migration at both subconfluent and confluent cell densities. We have previously reported that this difference in behaviour results from the secretion by fetal fibroblasts of a 'migration stimulating factor' (MSF) which is not made by their normal adult counterparts, and that MSF appears to act by stimulating the synthesis of hyaluronic acid (HA). Data presented in this communication indicate that (a) MSF specifically stimulates the synthesis of high molecular weight species of HA, (b) TGF-beta 1 inhibits the elevated migration of adult fibroblasts plated at subconfluent cell density, (c) under these conditions, TGF-beta 1 induces a parallel decrease in the synthesis of high molecular weight HA and increase in the synthesis of low molecular weight HA, (d) TGF-beta 1 is a potent antagonist of MSF, effectively blocking its stimulation of cell migration and synthesis of high molecular weight HA, and (e) the inhibition of fibroblast migration by TGF-beta 1 does not appear to be a chemotactic response dependent upon the existence of a concentration gradient of the cytokine. Our observations regarding the inhibitory effects of TGF-beta 1 on fibroblast migration into 3D collagen gels stand in marked contrast to various published reports indicating that this cytokine stimulates the migration of human skin fibroblasts through the pores of polycarbonate filters as used in modified Boyden chamber assays; this discrepancy underscores the importance of the substratum in modulating cellular response to cytokines. Our results are discussed in terms of the possible combined contribution of MSF and TGF-beta 1 to wound healing.",
keywords = "Cell Movement/physiology, Cells, Cultured, Child, Preschool, Collagen, Cytokines/physiology, Dose-Response Relationship, Drug, Fibroblasts/cytology, Fibronectins, Gels, Humans, Hyaluronic Acid/biosynthesis, Male, Transforming Growth Factor beta/physiology, Wound Healing/physiology",
author = "I Ellis and Grey, {A M} and Schor, {A M} and Schor, {S L}",
year = "1992",
month = "7",
language = "English",
volume = "102",
pages = "447--56",
journal = "Journal of Cell Science",
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Antagonistic effects of TGF-beta 1 and MSF on fibroblast migration and hyaluronic acid synthesis : Possible implications for dermal wound healing. / Ellis, I; Grey, A M; Schor, A M; Schor, S L.

In: Journal of Cell Science, Vol. 102, No. 3, 07.1992, p. 447-56.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Antagonistic effects of TGF-beta 1 and MSF on fibroblast migration and hyaluronic acid synthesis

T2 - Possible implications for dermal wound healing

AU - Ellis, I

AU - Grey, A M

AU - Schor, A M

AU - Schor, S L

PY - 1992/7

Y1 - 1992/7

N2 - The migration of adult skin fibroblasts into three-dimensional collagen gel matrices is differentially affected by cell density, with subconfluent cells displaying a significantly elevated level of migration compared to confluent ones. Fetal fibroblasts differ from adult cells in that they display an elevated level of migration at both subconfluent and confluent cell densities. We have previously reported that this difference in behaviour results from the secretion by fetal fibroblasts of a 'migration stimulating factor' (MSF) which is not made by their normal adult counterparts, and that MSF appears to act by stimulating the synthesis of hyaluronic acid (HA). Data presented in this communication indicate that (a) MSF specifically stimulates the synthesis of high molecular weight species of HA, (b) TGF-beta 1 inhibits the elevated migration of adult fibroblasts plated at subconfluent cell density, (c) under these conditions, TGF-beta 1 induces a parallel decrease in the synthesis of high molecular weight HA and increase in the synthesis of low molecular weight HA, (d) TGF-beta 1 is a potent antagonist of MSF, effectively blocking its stimulation of cell migration and synthesis of high molecular weight HA, and (e) the inhibition of fibroblast migration by TGF-beta 1 does not appear to be a chemotactic response dependent upon the existence of a concentration gradient of the cytokine. Our observations regarding the inhibitory effects of TGF-beta 1 on fibroblast migration into 3D collagen gels stand in marked contrast to various published reports indicating that this cytokine stimulates the migration of human skin fibroblasts through the pores of polycarbonate filters as used in modified Boyden chamber assays; this discrepancy underscores the importance of the substratum in modulating cellular response to cytokines. Our results are discussed in terms of the possible combined contribution of MSF and TGF-beta 1 to wound healing.

AB - The migration of adult skin fibroblasts into three-dimensional collagen gel matrices is differentially affected by cell density, with subconfluent cells displaying a significantly elevated level of migration compared to confluent ones. Fetal fibroblasts differ from adult cells in that they display an elevated level of migration at both subconfluent and confluent cell densities. We have previously reported that this difference in behaviour results from the secretion by fetal fibroblasts of a 'migration stimulating factor' (MSF) which is not made by their normal adult counterparts, and that MSF appears to act by stimulating the synthesis of hyaluronic acid (HA). Data presented in this communication indicate that (a) MSF specifically stimulates the synthesis of high molecular weight species of HA, (b) TGF-beta 1 inhibits the elevated migration of adult fibroblasts plated at subconfluent cell density, (c) under these conditions, TGF-beta 1 induces a parallel decrease in the synthesis of high molecular weight HA and increase in the synthesis of low molecular weight HA, (d) TGF-beta 1 is a potent antagonist of MSF, effectively blocking its stimulation of cell migration and synthesis of high molecular weight HA, and (e) the inhibition of fibroblast migration by TGF-beta 1 does not appear to be a chemotactic response dependent upon the existence of a concentration gradient of the cytokine. Our observations regarding the inhibitory effects of TGF-beta 1 on fibroblast migration into 3D collagen gels stand in marked contrast to various published reports indicating that this cytokine stimulates the migration of human skin fibroblasts through the pores of polycarbonate filters as used in modified Boyden chamber assays; this discrepancy underscores the importance of the substratum in modulating cellular response to cytokines. Our results are discussed in terms of the possible combined contribution of MSF and TGF-beta 1 to wound healing.

KW - Cell Movement/physiology

KW - Cells, Cultured

KW - Child, Preschool

KW - Collagen

KW - Cytokines/physiology

KW - Dose-Response Relationship, Drug

KW - Fibroblasts/cytology

KW - Fibronectins

KW - Gels

KW - Humans

KW - Hyaluronic Acid/biosynthesis

KW - Male

KW - Transforming Growth Factor beta/physiology

KW - Wound Healing/physiology

M3 - Article

C2 - 1506427

VL - 102

SP - 447

EP - 456

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - 3

ER -