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.
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Authors
Rouleau C, Rico C, Hapkova I, de Santa Barbara P
Institution
INSERM 1046 Unit, Médecine expérimentale Coeur et muscle, Montpellier University Hospital, 371 avenue du Doyen gaston Giraud, 34295 Montpellier, France. r-caroline@hotmail.fr
Source
Experimental and molecular pathology 93:1 2012 Aug pg 56-60MeSH
ActinsBone Morphogenetic Proteins
Carrier Proteins
Cells, Cultured
Desmin
Endometriosis
Female
Humans
Hysterectomy
Immunohistochemistry
Leiomyoma
Microfilament Proteins
Muscle Proteins
Muscle, Smooth
Myometrium
Progesterone
Signal Transduction
Smad1 Protein
Smad5 Protein
Uterine Neoplasms
Pub Type(s)
Journal ArticleResearch Support, Non-U.S. Gov't
Language
eng
PubMed ID
22537545
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