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

2.50
Hdl Handle:
http://hdl.handle.net/10541/108926
Title:
Antagonistic effects of TGF-beta 1 and MSF on fibroblast migration and hyaluronic acid synthesis. Possible implications for dermal wound healing.
Authors:
Ellis, I; Grey, A M; Schor, Ana M; Schor, Seth L
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.
Affiliation:
Department of Cell and Structural Biology, University of Manchester, UK.
Citation:
Antagonistic effects of TGF-beta 1 and MSF on fibroblast migration and hyaluronic acid synthesis. Possible implications for dermal wound healing. 1992, 102 ( Pt 3):447-56 J. Cell. Sci.
Journal:
Journal of Cell Science
Issue Date:
Jul-1992
URI:
http://hdl.handle.net/10541/108926
PubMed ID:
1506427
Type:
Article
Language:
en
ISSN:
0021-9533
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorEllis, Ien
dc.contributor.authorGrey, A Men
dc.contributor.authorSchor, Ana Men
dc.contributor.authorSchor, Seth Len
dc.date.accessioned2010-08-03T11:26:57Z-
dc.date.available2010-08-03T11:26:57Z-
dc.date.issued1992-07-
dc.identifier.citationAntagonistic effects of TGF-beta 1 and MSF on fibroblast migration and hyaluronic acid synthesis. Possible implications for dermal wound healing. 1992, 102 ( Pt 3):447-56 J. Cell. Sci.en
dc.identifier.issn0021-9533-
dc.identifier.pmid1506427-
dc.identifier.urihttp://hdl.handle.net/10541/108926-
dc.description.abstractThe 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.en
dc.language.isoenen
dc.subject.meshCell Movement-
dc.subject.meshCells, Cultured-
dc.subject.meshChild, Preschool-
dc.subject.meshCollagen-
dc.subject.meshCytokines-
dc.subject.meshDose-Response Relationship, Drug-
dc.subject.meshFibroblasts-
dc.subject.meshGels-
dc.subject.meshHumans-
dc.subject.meshHyaluronic Acid-
dc.subject.meshMale-
dc.subject.meshTransforming Growth Factor beta-
dc.subject.meshWound Healing-
dc.titleAntagonistic effects of TGF-beta 1 and MSF on fibroblast migration and hyaluronic acid synthesis. Possible implications for dermal wound healing.en
dc.typeArticleen
dc.contributor.departmentDepartment of Cell and Structural Biology, University of Manchester, UK.en
dc.identifier.journalJournal of Cell Scienceen
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