Tyrosine phosphorylation levels in primary human myometrial cells

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.