Abstract
Store-operated calcium (Ca2+) entry (SOCE) can be mediated by two novel proteins, STIM/Orai. We have previously demonstrated that members of the TRPC family, putative basal and store operated calcium entry channels, are present in human myometrium and regulated by labor associated stimuli IL-1β and mechanical stretch. Although STIM and Orai isoforms (1-3) have been reported in other smooth muscle cell types, there is little known about the expression or gestational regulation of STIM and Orai expression in human myometrium. Total RNA was isolated from lower segment human myometrial biopsies obtained at Cesarean section from women at the time of preterm no labor (PTNL), preterm labor (PTL), term non-labor (TNL), and term with labor (TL); primary cultured human uterine smooth muscle cells, and a human myometrial cell line (hTERT-HM). STIM1-2, and Orai1-3 mRNA expression was assessed by quantitative real-time PCR. All five genes were expressed in myometrial tissue and cultured cells. STIM1-2 and Orai2-3 expression was significantly lower in cultured cells compared tissue. This has implications with regard investigation of the contribution of these proteins in cultured cells. Orai2 was the most abundant Orai isoform in human myometrium. Expression of STIM1-2/Orai1-3 did not alter with the onset of labor. Orai1 mRNA expression in cultured cells was enhanced by IL-1β treatment. This novel report of STIM1-2 and Orai1-3 mRNA expression in pregnant human myometrium and Orai1 regulation by IL-1β indicates a potential role for these proteins in calcium signaling in human myometrium during pregnancy.
Highlights
Intracellular calcium signals regulate a variety of important physiological processes including gene transcription, cell growth, and contraction
Orai3 expression was significantly higher in myometrial tissue than cultured cells with hTERT-HM exhibiting the lowest level of expression
In the present study, we have clearly demonstrated that STIM and Orai isoforms are expressed in pregnant human myometrial tissue
Summary
Intracellular calcium signals regulate a variety of important physiological processes including gene transcription, cell growth, and contraction. In excitable cells, including myometrium, calcium entry via voltage-gated calcium channels form the predominant calcium entry pathway involved in contraction, but there is evidence for functional SOCE and ROCE in myometrial tissue and cells (Sanborn, 1995, 2007a,b; Tribe, 2001; Dalrymple et al, 2004, 2007; Shmygol and Wray, 2004; Noble et al, 2009) We hypothesized that these pathways may contribute to prolongation of contraction events, and to uterine smooth muscle growth and provision of discrete calcium signals required to modulate gene expression throughout gestation and at labor onset. We have shown that TRPC3 expression is up-regulated by mechanical strain and the pro-inflammatory cytokine IL-1β, stimulators of myometrial growth and activation, in cultured human myometrial cells (Dalrymple et al, 2004, 2007)
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