TRPC3 Overexpression Promotes the Progression of Inflammation-Induced Preterm Labor and Inhibits T Cell Activation

Abstract

Background/Aims: To detect the expression of the TRPC3 channel protein in the tissues of women experiencing preterm labor and investigate its interaction with T lymphocytes, providing a theoretical basis for the clinical prevention of threatened preterm labor and the development of drug-targeted therapy. Methods: Forty-seven women experiencing preterm labor and 47 women experiencing normal full-term labor were included in this study. All included women underwent delivery via cesarean section; uterine samples were obtained at delivery. The expression of TRPC3 in uterine tissue was detected by immunohistochemistry, real-time quantitative reverse transcription-PCR, and western blot assay. Activation of T lymphocytes in peripheral blood and uterine tissue were detected by flow cytometry. A TRPC3^-/- mouse model of inflammation-induced preterm labor was established; expression of TRPC3, Cav3.1, and Cav3.2 were analyzed in mouse uterine tissue. Activation of T lymphocytes in female mouse and human peripheral blood samples was determined using flow cytometry. Results: In women experiencing preterm labor, expression of TRPC3 and the Cav3.1 and Cav3.2 proteins was significantly increased; in addition, the percentage of CD3⁺, CD4⁺, and CD8⁺ T cells in peripheral blood was significantly decreased. TRPC3 knockout significantly delayed the occurrence of preterm labor in mice. The muscle tension of ex vivo uterine strips was lower, Cav3.1 and Cav3.2 protein expression was lower, and the percentage of CD8⁺ T lymphocytes was significantly increased in wild-type mice subjected to an inflammation-induced preterm labor than in wild-type mice experiencing normal full-term labor. Conclusion: TRPC3 is closely related to the initiation of labor. TRPC3 relies on Cav3.1 and Cav3.2 proteins to inhibit inflammation-induced preterm labor by inhibiting the activation of T cells, in particular CD8⁺ T lymphocytes.

Inhibitory effect of Pyr6 (an Orai channel blocker) on agonist‐induced contractions in rat uterus

“…18,20,21 Also described in derived cell lines of human myometrium, are TRPCs, Orai, and STIM. 19,20,22,23,[34][35][36] Our results in rat myometrium also indicated that Orai1 channels participate in the maintenance of muscarinic agonist-induced action. Molecular evidence of [Ca 2+ ]i elevation, promoted by the activation of muscarinic receptors and mediated by Orai1 channels, has been obtained for some cell types.…”

Functional expression of the mechanosensitive PIEZO1 channel in primary endometrial epithelial cells and endometrial organoids

“…Studies assessing the underlying molecular mechanisms behind the embryo-uterine interplay are very scarce and molecular candidates involved in the early communication still need to be fully elucidated and characterized. Ion channels are potential candidates to govern signals and are emerging more often as important players in the field of reproductive medicine 42,43 . However, the fingerprint of ion channels in endometrial epithelial cells is very incomplete.…”

Progesterone receptor isoform B regulates the Oxtr - Plcl2 - Trpc3 pathway to suppress uterine contractility

“…These findings reveal the role of phospholipase C-like proteins in suppressing uterine smooth muscle contraction with a human relevance. In summary, our data show the PGR-B-specific modulation on multiple regulators in a signaling cascade for muscle contraction that includes the oxytocin receptor, the phospholipase C signaling, and a calcium channel of known contribution on laboring (69,71,74).…”