title: An alternative role of C1q in cell migration and tissue remodeling: contribution to trophoblast invasion and placental development.
abstract: Fetal trophoblast cells invading the decidua in the early phase of pregnancy establish complex interaction with the maternal extracellular matrix. We discovered that C1q was widely distributed in human decidual stroma in the absence of C4 and C3 and was actively synthesized by migrating extravillous trophoblasts. The cells expressed the messages for the three chains of C1q and secreted this complement component that interacted with the proteins of the decidual extracellular matrix. Solid phase-bound C1q promoted trophoblast adhesion and migration, and cell binding to C1q resulted in activation of ERK1/2 MAPKs. Ab inhibition experiments showed that the receptors for the globular head of C1q/p33 and α(4)β(1) integrin were both involved in this process and were colocalized on the cell surface following binding of C1q to trophoblasts. We also found that C1q(-/-) mice manifested increased frequency of fetal resorption, reduced fetal weight, and smaller litter sizes compared with wild-type mice. C1q deficiency was associated with impaired labyrinth development and decidual vessel remodeling. Collectively, these data suggest that C1q plays an important role in promoting trophoblast invasion of decidua and that defective local production of C1q may be involved in pregnancy disorders, such as pre-eclampsia, characterized by poor trophoblast invasion.
authors.affiliation: Department of Life Sciences, for Maternal and Child Health, Burlo Garofolo, University of Trieste, Trieste, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Agostinis
authors.forename: Roberta
authors.initials: R
authors.lastname: Bulla
authors.forename: Claudio
authors.initials: C
authors.lastname: Tripodo
authors.forename: Angela
authors.initials: A
authors.lastname: Gismondi
authors.forename: Helena
authors.initials: H
authors.lastname: Stabile
authors.forename: Fleur
authors.initials: F
authors.lastname: Bossi
authors.forename: Carla
authors.initials: C
authors.lastname: Guarnotta
authors.forename: Cecilia
authors.initials: C
authors.lastname: Garlanda
authors.forename: Francesco
authors.initials: F
authors.lastname: De Seta
authors.forename: Paola
authors.initials: P
authors.lastname: Spessotto
authors.forename: Angela
authors.initials: A
authors.lastname: Santoni
authors.forename: Berhane
authors.initials: B
authors.lastname: Ghebrehiwet
authors.forename: Guillermina
authors.initials: G
authors.lastname: Girardi
authors.forename: Francesco
authors.initials: F
authors.lastname: Tedesco
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D015922:Complement C1q / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D010929:Placentation / Q000276:immunology*; D011225:Pre-Eclampsia / Q000276:immunology; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014327:Trophoblasts / Q000276:immunology / Q000378:metabolism*
chemical_list: D015922:Complement C1q