title: Immunohistochemical analysis of bone morphological protein signaling pathway in human myometrium.
abstract: We assessed by immunohistochemistry the expression of the phosphorylated (activated) form of Smad1 and 5 (P-SMAD1/5), of Noggin and of two smooth muscle cell markers (α-SMA and SM22) in a series of human myometrium samples and in a smooth muscle cell line derived from human myometrium (HUt-SMC, PromoCell, USA). Myometrium samples were removed from two cadavers (a fetus at 26 weeks of gestation and a neonate) and from ten non-menopausal women who underwent hysterectomy for adenomyosis and leiomyoma. P-SMAD1/5 expression was never detected in myometrium (both normal and pathological specimens), but only as a nuclear positive staining in glandular and luminal epithelial cells in sections in which also the endometrial mucosa was present. Noggin was strongly expressed especially in myometrium and adenomyosis samples from non-menopausal patients in comparison to the neonatal and fetal myometrium specimens in which muscle cells were less positive. In more than 95% of HUt-SMCs, α-SMA and Desmin were co-expressed, indicating a pure smooth muscle phenotype. When progesterone was added to the culture medium, no P-SMAD1/5 expression was detected, whereas the expression Noggin and SM22, a marker of differentiated smooth muscle cells, increased by 3 fold (p=0.002) and 4.3 fold (p=0.001), respectively (p=0.002). Our results suggest that, in non-menopausal normal human myometrium, the BMP pathway might be inhibited and that this inhibition might be enhanced by progesterone, which increases the differentiation of smooth muscle cells (SM22 levels). These findings could help in the identification of new mechanisms that regulate uterine motility.
authors.affiliation: INSERM 1046 Unit, Médecine expérimentale Coeur et muscle, Montpellier University Hospital, 371 avenue du Doyen gaston Giraud, 34295 Montpellier, France. r-caroline@hotmail.fr
authors.forename: Caroline
authors.initials: C
authors.lastname: Rouleau
authors.forename: Caroline
authors.initials: C
authors.lastname: Rico
authors.forename: Ilona
authors.initials: I
authors.lastname: Hapkova
authors.forename: Pascal
authors.initials: P
authors.lastname: de Santa Barbara
mesh_terms: D000199:Actins / Q000096:biosynthesis; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis; D002478:Cells, Cultured; D003893:Desmin / Q000096:biosynthesis; D004715:Endometriosis / Q000378:metabolism; D005260:Female; D006801:Humans; D007044:Hysterectomy; D007150:Immunohistochemistry; D007889:Leiomyoma / Q000378:metabolism; D008840:Microfilament Proteins / Q000096:biosynthesis; D009124:Muscle Proteins / Q000096:biosynthesis; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D051898:Smad1 Protein / Q000096:biosynthesis; D051902:Smad5 Protein / Q000096:biosynthesis; D014594:Uterine Neoplasms / Q000378:metabolism; D000099176:Noggin Protein
chemical_list: D000199:Actins; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D003893:Desmin; D008840:Microfilament Proteins; D009124:Muscle Proteins; D011374:Progesterone; D051898:Smad1 Protein; D051902:Smad5 Protein; D000099176:Noggin Protein; C541116:ACTA2 protein, human; C497399:SMAD1 protein, human; C497797:SMAD5 protein, human; C051615:transgelin