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BOR - Papers in Press, published online ahead of print May 7, 2008.
Biol Reprod 2008, 10.1095/biolreprod.108.068338
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BIOLOGY OF REPRODUCTION 79, 348–355 (2008)
DOI: 10.1095/biolreprod.108.068338
© 2008 by the Society for the Study of Reproduction, Inc.

research-article

Surfactant Protein A Signaling Pathways in Human Uterine Smooth Muscle Cells1

Ignacio Garcia-Verdugo 3, Zahra Tanfin 3, Emmanuelle Dallot 4, Marie-Josèphe Leroy 4, and Michelle Breuiller-Fouché 2 4

Equipe Signalisation et Régulations Cellulaires,3 Institut de Biochimie et Biophysique Moléculaire et Cellulaire, CNRS, UMR-8619, Université Paris-Sud, 91400 Orsay, France INSERM,4 U767, Faculté des Sciences Pharmaceutiques et Biologiques, Université René Descartes, 75006 Paris, France

ABSTRACT

The present study investigated the ability of surfactant associated protein A1 (SFTPA1), a major component of lung surfactant, to bind and serve as a signal in human cultured myometrial cells. By using ligand blot analysis with 125I-SFTPA1, we consistently identified two myometrial SFTPA1 interacting proteins (55 and 200 kDa). We found that the SFTPA1 immunoreactive protein was present in myometrial cells. We also showed by indirect immunofluorescence the nuclear translocation of RELA (also known as NFkappaB p65 subunit) after activation of myometrial cells by SFTPA1. Neutralization of TLR4 did not reverse this effect. Moreover, SFTPA1 rapidly activated mitogen-activated protein kinase 1/3 (MAPK1/3) and protein kinase C zeta (PRKCZ). The prolonged treatment of myometrial cells with SFTPA1 upregulated PTGS2 (COX2) protein levels. We next evaluated whether SFTPA1 affected the actin dynamic. Stimulation of myometrial cells with SFTPA1 markedly enhanced the intensity of the filamentous-actin pool stained with fluorescein isothiocyanate-phalloidin. Inhibition of PRKC or Rho-associated, coiled-coil containing protein kinase 1 (ROCK) reduced the SFTPA1-mediated stress fiber formation. Our data support the hypothesis that human myometrial cells express functional SFTPA1 binding sites and respond to SFTPA1 to initiate activation of signaling events related to human parturition.

mechanisms of hormone action, myometrium, signal transduction, surfactant protein A, pregnancy, parturition, uterus

FOOTNOTES

1Supported by grants from the Fondation de la Recherche Médicale and the Marie Curie Programme "Pulmo-Net" (MRTN-CT 2004-512229).

Correspondence: 2Michelle Breuiller-Fouché, INSERM U767, Faculté de Pharmacie, 4 avenue de l'Observatoire, 75270, Paris cedex 06, France. FAX: 33 1 40 48 83 94; e-mail: michelle.breuiller-fouche{at}inserm.fr






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Copyright © 2008 by the Society for the Study of Reproduction.