title: The importance of fibroblasts in remodelling of the human uterine cervix during pregnancy and parturition.
abstract: It is well established that fibroblasts play a crucial role in pathophysiological extracellular matrix remodelling. The aim of this project is to elucidate their role in normal physiological remodelling. Specifically, the remodelling of the human cervix during pregnancy, resulting in an enabled passage of the child, is used as the model system. Fibroblast cultures were established from cervices of non-pregnant women, women after 36 weeks of pregnancy and women directly after partus. The cells were immunostained and quantified by western blots for differentiation markers. The cultures were screened for cytokine and metalloproteinase production and characterized by global proteome analysis. The cell cultures established from partal donors differ significantly from those from non-pregnant donors, which is in accordance with in vivo findings. A decrease in alpha-smooth actin and prolyl-4-hydroxylase and an increase in interleukin (IL)-6, IL-8 and matrix metalloproteinases (MMP)-1 and MMP-3 were observed in cultures from partal donors. 2D-gel electrophoresis followed by mass spectrometry showed that the expression of 59 proteins was changed significantly in cultures of partal donors. The regulated proteins are involved in protein kinase C signalling, Ca2+ binding, cytoskeletal organization, angiogenesis and degradation. Our data suggest that remodelling of the human cervix is orchestrated by fibroblasts, which are activated or recruited by the inflammatory processes occurring during the ripening cascade.
authors.affiliation: Department of Experimental Medical Science, BMC, Lund University, Lund, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Malmström
authors.forename: Maria
authors.initials: M
authors.lastname: Sennström
authors.forename: Anna
authors.initials: A
authors.lastname: Holmberg
authors.forename: Helena
authors.initials: H
authors.lastname: Frielingsdorf
authors.forename: Erik
authors.initials: E
authors.lastname: Eklund
authors.forename: Lars
authors.initials: L
authors.lastname: Malmström
authors.forename: Ellen
authors.initials: E
authors.lastname: Tufvesson
authors.forename: Maria F
authors.initials: MF
authors.lastname: Gomez
authors.forename: Gunilla
authors.initials: G
authors.lastname: Westergren-Thorsson
authors.forename: Gunvor
authors.initials: G
authors.lastname: Ekman-Ordeberg
authors.forename: Anders
authors.initials: A
authors.lastname: Malmström
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D003599:Cytoskeleton / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D013058:Mass Spectrometry; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D018919:Neovascularization, Physiologic; D036801:Parturition / Q000378:metabolism / Q000502:physiology*; D011247:Pregnancy; D011493:Protein Kinase C / Q000378:metabolism; D040901:Proteomics
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D016209:Interleukin-8; D011493:Protein Kinase C; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1; D002118:Calcium