Surfactant protein A signaling pathways in human uterine smooth muscle cells.
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.
Garcia-Verdugo
Ignacio
I
Equipe Signalisation et Régulations Cellulaires, Institut de Biochimie et Biophysique Moléculaire et Cellulaire, CNRS, UMR-8619, Université Paris-Sud, 91400 Orsay, France.
Tanfin
Zahra
Z
Dallot
Emmanuelle
E
Leroy
Marie-Josèphe
MJ
Breuiller-Fouché
Michelle
M
D008841:Actin Cytoskeleton / Q000378:metabolism; D021581:Active Transport, Cell Nucleus; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005260:Female; D006801:Humans; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D009215:Myometrium / Q000378:metabolism*; D036801:Parturition / Q000378:metabolism / Q000502:physiology; D010766:Phosphorylation; D011247:Pregnancy; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism; D037662:Pulmonary Surfactant-Associated Protein A / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D051996:Transcription Factor RelA / Q000378:metabolism; D014599:Uterus / Q000378:metabolism*; D000099221:Protein Kinase C zeta
D051546:Cyclooxygenase 2; D048052:Mitogen-Activated Protein Kinase 3; D011493:Protein Kinase C; D037662:Pulmonary Surfactant-Associated Protein A; D051996:Transcription Factor RelA; D000099221:Protein Kinase C zeta; C498143:RELA protein, human; C445842:SFTPA1 protein, human; C496540:PTGS2 protein, human