Progesterone and Gravidity Differentially Regulate Expression of Extracellular Matrix Components in the Pregnant Rat Myometrium1

Shynlova, Oksana; Mitchell, Jennifer A.; Tsampalieros, Anne; Langille, B. Lowell; Lye, Stephen J.

doi:10.1095/biolreprod.103.023648

Cited by 108 publications

(112 citation statements)

References 33 publications

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“…In our study, artificial maintenance of elevated P4 levels at late gestation (from day 20 to day 23) by daily injections of hormone caused a failure to initiate labor. We showed before that this treatment prevented the increase in the expression of CAPs, AP-1, and ECM genes in the rat myometrium (Piersanti & Lye 1995, Shynlova et al 2004. We have now shown that the administration of P4 also prevented the increase of Tgfb3 mRNA levels at term when compared with vehicle-treated animals (Fig.…”

Section: Figure 1 Illustrates the Expression Ofmentioning

confidence: 51%

“…TGFb3 treatment was also found to stimulate fibronectin expression in human cultured leiomyoma cells (Arici & Sozen 2000). We have reported earlier that expression of fibronectin, as well as major components of basement membrane, namely type IV collagen and laminin, are dramatically TGFb in pregnant myometrium up-regulated prior to and during labor in rats (Shynlova et al 2004). Thus, the parallel increase of TGFb3 and ECM components at late gestation suggests that TGFb3 may mediate ECM induction, providing the mechanism to anchor hypertrophied uterine myocytes in order to produce coordinated, forceful labor contractions.…”

Section: Discussionmentioning

confidence: 70%

“…We have shown that the timely expression of putative CAPs (Cx43, oxytocin receptor, prostaglandin receptor) is regulated by the integration of fetal endocrine and growth signals underlying myometrial activation (Ou et al 1997(Ou et al , 1998. In addition, we have reported that the activation of CAP genes at term correlated with the increase in extracellular matrix (ECM) protein expression (Shynlova et al 2004). It has been reported by others that the CAP and ECM expression could be regulated by cytokines, such as TGFb1, which may play a role in preparing the myometrium for parturition (Hatthachote et al 1998).…”

Section: Introductionmentioning

confidence: 99%

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

Shynlova

Tsui²,

Dorogin³

et al. 2007

Reproduction

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From a quiescent state in early pregnancy to a highly contractile state in labor, the myometrium displays tremendous growth and remodeling. We hypothesize that the transforming growth factor b (TGFb) system is involved in the differentiation of pregnant myometrium throughout gestation and labor. Furthermore, we propose that during pregnancy the mechanical and hormonal stimuli play a role in regulating myometrial TGFbs. The expression of TGFb1-3 mRNAs and proteins was examined by real-time PCR, Western immunoblot, and localized with immunohistochemistry in the rat uterus throughout pregnancy and labor. Tgfb1-3 genes were expressed differentially in pregnant myometrium. Tgfb2 gene was not affected by pregnancy, whereas the Tgfb1 gene showed a threefold increase during the second half of gestation. In contrast, we observed a dramatic bimodal change in Tgfb3 gene expression throughout pregnancy. Tgfb3 mRNA levels first transiently increased at mid-gestation (11-fold on day 14) and later at term (45-fold at labor, day 23). Protein expression levels paralleled the changes in mRNA. Treatment of pregnant rats with the progesterone (P4) receptor antagonist RU486 induced premature labor on day 19 and increased Tgfb3 mRNA, whereas artificial maintenance of elevated P4 levels at late gestation (days 20-23) caused a significant decrease in the expression of Tgfb3 gene. In addition, Tgfb3 was up-regulated specifically in the gravid horn of unilaterally pregnant rats subjected to a passive biological stretch imposed by the growing fetuses, but not in the empty horn. Collectively, these data indicate that the TGFb family contributes in the regulation of myometrial activation at term integrating mechanical and endocrine signals for successful labor contraction. Reproduction (2007) 134 503-511

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Section: Figure 1 Illustrates the Expression Ofmentioning

confidence: 51%

Section: Discussionmentioning

confidence: 70%

Section: Introductionmentioning

confidence: 99%

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

Shynlova

Tsui²,

Dorogin³

et al. 2007

Reproduction

Self Cite

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“…18S rRNA is constitutively expressed in rat myometrial cells and has been utilized, in the past, as a loading control for analysis of myometrial gene expression (Mitchell & Lye 2002, Shynlova et al 2004.…”

Section: Northern Blot Hybridizationmentioning

confidence: 99%

Small heat shock protein 27 (Hsp27) expression is highly induced in rat myometrium during late pregnancy and labour

White¹,

Williams²,

Highmore³

et al. 2005

Reproduction

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The underlying mechanisms that regulate uterine contractions during labour are still poorly understood. A candidate regulatory protein is heat shock protein 27 (Hsp27). It belongs to the small heat shock protein family and can regulate actin cytoskeleton dynamics, act as a chaperone, and may regulate contractile protein activation. As a result, we hypothesized that Hsp27 expression would be highly induced during late pregnancy and labour. Hsp27 mRNA expression was significantly elevated (P < 0.05) on days 17 to 22 of gestation. In addition, immunoblot analysis demonstrated that detection of total Hsp27 increased (P < 0.05) between day 21 and 1 day post-partum (PP) inclusive. Since phosphorylation of Hsp27 has been reported to be a prerequisite for smooth muscle contraction, we examined the temporal and spatial expression of Ser-15 phosphorylated Hsp27. Immunoblot analysis showed that the detection of Ser-15 phosphorylated Hsp27 significantly increased (P < 0.05) between days 19 and 23 (active labour) inclusive, in parallel with detection of total Hsp27. Immunocytochemical analysis of Ser-15 phosphorylated Hsp27 expression in situ demonstrated that phosphorylated Hsp27 in circular muscle became detectable in peri-nuclear and membrane regions on days 19 to 22, but was primarily restricted to the cytoplasm on days 23 to PP. In contrast, phosphorylated Hsp27 in longitudinal muscle was primarily detected in myocyte membranes on days 15 to 22, and then also became detectable in the cytoplasm of myocytes on days 23 and PP. Our results demonstrate that Hsp27 expression is highly upregulated during late pregnancy and labour and suggest that Hsp27 is a potential candidate contraction-associated protein.

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“…Myometrial cells increase in number and the expression of anti-apoptotic factors, including BCL2, is increased within these cells contributing to an overall increase in proliferation (Shynlova et al 2006). The next phase is the synthetic phase from D15 to D21, where the protein:DNA ratio in the myometrium is increased, cells hypertrophy and increase their production of interstitial extracellular matrix proteins (ECM) and remodel focal adhesions (MacPhee & Lye 2000, Shynlova et al 2004. In the contractile phase, there is an increased expression of basement membrane matrix proteins such as fibronectin and associated integrin receptors in myometrial cells (Shynlova et al 2004, Williams et al 2005, 2010.…”

Section: Introductionmentioning

confidence: 99%

Induction of expression and phosphorylation of heat shock protein B5 (CRYAB) in rat myometrium during pregnancy and labour

et al. 2016

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During pregnancy the myometrium undergoes a programme of differentiation induced by endocrine, cellular, and biophysical inputs. Small heat shock proteins (HSPs) are a family of ten (B1-B10) small-molecular-weight proteins that not only act as chaperones, but also assist in processes such as cytoskeleton rearrangements and immune system activation. Thus, it was hypothesized that HSPB5 (CRYAB) would be highly expressed in the rat myometrium during the contractile and labour phases of myometrial differentiation when such processes are prominent. Immunoblot analysis revealed that myometrial CRYAB protein expression significantly increased from day (D) 15 to D23 (labour; P < 0.05). In correlation with these findings, serine 59-phosphorylated (pSer59) CRYAB protein expression significantly increased from D15 to D23, and was also elevated 1-day post-partum (P < 0.05). pSer59-CRYAB was detected in the cytoplasm of myocytes within both uterine muscle layers mid-to late-pregnancy. In unilaterally pregnant rats, pSer59-CRYAB protein expression was significantly elevated in the gravid uterine horns at both D19 and D23 of gestation compared with non-gravid horns. Co-immunolocalization experiments using the hTERT-human myometrial cell line and confocal microscopy demonstrated that pSer59-CRYAB co-localized with the focal adhesion protein FERMT2 at the ends of actin filaments as well as with the exosomal marker CD63. Overall, pSer59-CRYAB is highly expressed in myometrium during late pregnancy and labour and its expression appears to be regulated by uterine distension. CRYAB may be involved in the regulation of actin filament dynamics at focal adhesions and could be secreted by exosomes as a prelude to involvement in immune activation in the myometrium.Reproduction (2016) 152 69-79

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Progesterone and Gravidity Differentially Regulate Expression of Extracellular Matrix Components in the Pregnant Rat Myometrium1

Cited by 108 publications

References 33 publications

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

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

Small heat shock protein 27 (Hsp27) expression is highly induced in rat myometrium during late pregnancy and labour

Induction of expression and phosphorylation of heat shock protein B5 (CRYAB) in rat myometrium during pregnancy and labour

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