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Tyrosine phosphorylation levels in primary human myometrial cells

Citation

Gao, Lu (2019), Tyrosine phosphorylation levels in primary human myometrial cells, Dryad, Dataset, https://doi.org/10.5061/dryad.jh9w0vt6m

Abstract

Context. Preterm birth is one of the most common complications during human pregnancy and labor, and associated with a dramatic switch within the uterus from quiescence to contractility. However, the mechanisms underlying uterine remodeling are largely unknown.

Objective. To define the roles of src-homology phosphatase type-1 (SHP-1, PTPN6) in regulating the phosphorylation of proteins involved in the uterine smooth muscle cell functions.

Design and Setting. Human myometrial tissues, primary uterine smooth muscle cells, and myometrium-specific Ptpn6-KO mice were used to study SHP-1 regulation of uterine remodeling and labor.

Patients. Patients who underwent elective cesarean section (n=20) and emergency cesarean section at term (37-42 wks, n=20) were recruited with no evidence of underlying diseases.

Results. We found that SHP-1 was significantly decreased in human myometrium in labor compared with that not in labor. Timed-pregnant mice injected intraperitoneally with the specific SHP-1 inhibitor, PTPI-1, or those with a myometrium-specific Ptpn6-KO manifested significantly preterm labor, with enriched plasmalemmal dense plaques between myometrial cells and increased phosphorylation at Tyr397 and Tyr576/577 sites of focal adhesion kinase (FAK), which remained to the time of labor. Knockdown of SHP-1 dramatically increased the spontaneous contraction of HUSMCs, which was reversed by co-infection of a FAK-knockdown lentivirus. PGF2a could downregulate SHP-1 via PI3K-NF-kB pathway.

Conclusions. SHP-1 plays important roles in uterine remodeling and plasticity by activating focal adhesion pathway. The aberrant decrease of SHP-1 may be one of the reasons for spontaneous preterm labor, and interventions for modulation of SHP-1 provide a potential strategy for preventing preterm birth.