Expression of α5 Integrin (Itga5) Is Elevated in the Rat Myometrium During Late Pregnancy and Labor: Implications for Development of a Mechanical Syncytium1

Abstract

The underlying mechanisms controlling uterine contractions during labor are still poorly understood. Integrins are heterodimeric, transmembrane receptors composed of alpha and beta subunits that can be found in focal adhesions. Because these structures play an important role in the regulation of smooth muscle contractility and cell adhesion, we hypothesized that alpha5 integrin mRNA (Itga5) and protein (ITGA5) expression would be induced in the rat myometrium during late pregnancy and labor. Itga5 mRNA expression was significantly increased (P < 0.05) from Day 17 to labor, noticeably decreasing 1 day postpartum (PP). Immunoblot analysis illustrated a continual increase in ITGA5 levels during pregnancy, labor, and PP, with levels reaching significance at labor (P < 0.05). Analysis of ITGA5 expression by immunocytochemistry demonstrated that it is primarily localized to myometrial cell membranes in the longitudinal muscle layer of the myometrium from before pregnancy to Day 6, and in both the longitudinal and circular muscle layers from Day 15 to PP. Treatment of late-pregnant rats with progesterone blocked labor and resulted in sustained expression of Itga5 mRNA expression to Day 24. In addition, immunocytochemistry experiments showed ITGA5 was detectable at higher levels in cell membranes of both myometrial layers in progesterone-treated animals on Days 23 and 24, compared with vehicle controls. We propose that ITGA5, with its sole known partner, ITGB1, may be important in promoting cellular cohesion during late pregnancy. This process may aid the development of a mechanical syncytium for efficient force transduction during the sustained, coordinated, and powerful contractions of labor.

Focal adhesion signaling is required for myometrial ERK activation and contractile phenotype switch before labor

“…But, expression of both integrins and syndecans is known to be elevated in myometrium during late pregnancy and labor [Cluff et al, 2005;Williams et al, 2005], suggesting a possible role of focal adhesion signaling in the regulation of myometrial contractility. In the present study, we have linked gestation-dependent myometrial ERK targeting with focal adhesion signaling.…”

“…Thus, FA have been postulated as mechano-sensors and sites for protein tyrosine kinase mediated signaling pathways [Burridge and Chrzanowska-Wodnicka, 1996]. However, few studies have been focused on this topic in the setting of pregnancy and labor [Macphee and Lye, 2000;Williams et al, 2005]. Studies from the Lye laboratory have suggested that endocrine pathways may not be sufficient alone to bring about myometrial activation for labor, and that additional pathways involving mechanical tension on the myometrium may also be involved [Macphee and Lye, 2000], but the signaling pathways linking mechanical forces to myometrial activation have not been delineated.…”

The expression of transforming growth factor β in pregnant rat myometrium is hormone and stretch dependent

“…Specific forward and reverse primers were designed using Primer Express software, version 2. (Williams et al 2005). Tubulin is present in almost all eukaryotic cells and is commonly used as a housekeeping protein (Vemuganti et al 2004).…”

Gene and protein expression in the myometrium in pregnancy and labor

“…In human term pregnant myometrium, changes in cytoskeletal organization support a role for FAK and other focal adhesion-associated proteins as regulators of actin dynamics. Fibronectin receptor-alpha subunit (ITGA5) with its known partner ITGB1, is up-regulated in rat myometrium during late pregnancy and labor (Williams et al 2005) as well as vitronectin receptoralpha polypeptide (ITGAV) in the TNIL human myometrium (Rehman et al 2003). Therefore they may interact with actin-binding proteins (e.g.…”