Effects of recombinant H2 relaxin on the expression of matrix metalloproteinases and tissue inhibitor metalloproteinase in cultured early placental extravillous trophoblasts

Maruo, Nobuyuki; Nakabayashi, Koji; Wakahashi, Senn; Yata, Ai; Maruo, Takeshi

doi:10.1007/s12020-008-9034-5

Cited by 11 publications

(10 citation statements)

References 33 publications

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“…In fact, its presence was associated with higher MMP-9/TIMP-1 molar ratios and with lower TIMP-1, in agreement with previous observations in other experimental contexts [20,21]. However, in our sample, relaxin did not differ between normotensive and hypertensive subjects, and BP levels did not differ between subjects with detectable and undetectable relaxin.…”

Section: Discussionsupporting

confidence: 92%

“…Besides, it modulates the release of other molecules, such as VEGF [19], or some MMPs and their inhibitors (tissue inhibitors of metalloproteinases; TIMPs) [20,21], and through this mechanism, it may participate in other functions, such as vascular remodeling [22]. In men, the prostate is the main source of relaxin, which may exert a paracrine action in the surrounding tissues [23].…”

Section: Introductionmentioning

confidence: 99%

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Relaxin in Obstructive Sleep Apnea: Relationship with Blood Pressure and Inflammatory Mediators

Bonanno

Riccobono²,

Bonsignore

et al. 2016

Respiration

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Background: Obstructive sleep apnea (OSA) is associated with nocturnal intermittent hypoxia, which may be responsible for increased circulating levels of vascular endothelial growth factor (VEGF) and inflammatory mediators, such as metalloproteinases (MMPs), and which contributes to the pathogenesis of systemic hypertension. Why some OSA patients remain normotensive is poorly understood. Relaxin-2, a pregnancy hormone, may sometimes circulate in men and could increase in hypoxic conditions. It exerts a vasodilatory activity and can modulate the release of molecules, such as MMPs and VEGF. Objectives: The objective of this study was to explore if circulating relaxin-2 in male OSA subjects may be related to OSA severity, to circulating levels of MMPs, of their inhibitors (tissue inhibitors of metalloproteinases; TIMPs), and of VEGF, and if it may protect from hypertension. Patients andMethods: Fifty untreated male subjects with suspected OSA were recruited. After nocturnal polysomnography, a morning venous blood sample was withdrawn. Then, 24-hour ambulatory blood pressure (BP) monitoring was performed. Results: The respiratory disturbance index in the sample was 30.4 [interquartile range (IQR) 15.6-55.2]. Relaxin-2 was detectable in 20 subjects. These subjects did not differ in OSA severity or diurnal and nocturnal BP from subjects with undetectable relaxin-2, but they showed lower TIMP-1 (126.8 ± 29.1 vs. 156.9 ± 41.7 pg/ml, respectively; p = 0.007) and a marginally higher MMP-9/TIMP-1 molar ratio [0.58 (IQR 0.23-1.35) vs. 0.25 (IQR 0.15-0.56); p = 0.052]. Conclusions: Relaxin-2 in male subjects was not related to OSA severity, but it was associated with lower TIMP-1. As it was often undetectable, even when BP values were normal, it is unlikely that it plays a role as a major factor protecting from hypertension in OSA.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Relaxin in Obstructive Sleep Apnea: Relationship with Blood Pressure and Inflammatory Mediators

Bonanno

Riccobono²,

Bonsignore

et al. 2016

Respiration

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“…In 2002, LGR7 and LGR8 were discovered to be the receptors for relaxin. Actually, we have demonstrated for the first time the presence of relaxin receptors (LGR7 and LGR8) in the human early placental EVTs [5]. In humans, three forms of relaxin have been identified: H1, H2 and H3 relaxin.…”

Section: Relaxin In the Regulation Of The Invasion Of Evtsmentioning

confidence: 87%

“…It seems that in humans, relaxin is both a systemic hormone secreted by the corpus luteum and an autocrine/paracrine hormone at the maternal-foetal interface formed by the decidua, placenta and foetal membranes. In our recent study to investigate the effects of recombinant H2 (rH2) relaxin on cultured early placental EVTs, treatment with rH2 relaxin increased MMP-2 and MMP-9 mRNA levels and decreased TIMP-1 mRNA levels in those cells (5). These results suggest that relaxin may promote the invasive potential of early placental EVTs by up-regulating MMP-2 and MMP-9 expression and down-regulating TIMP-1 expression through the interaction with relaxin receptors (LGR7 and LGR8) in EVTs.…”

Section: Relaxin In the Regulation Of The Invasion Of Evtsmentioning

confidence: 99%

Progesterone, thyroid hormone and relaxin in the regulation of the invasive potential of extravillous trophoblasts in early placental development

Maruo¹

2010

Gynecological Endocrinology

Self Cite

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“…92 Invading trophoblasts express gelatinase activity facilitating migration and invasion of the uterus. 93,94 Analogous to endothelial cell migration, 95 there are data, albeit more limited, suggesting that the ET B -receptor–endothelial NOS system promotes trophoblast migration and invasion. 96–98 Thus, all of the signaling components in the relaxin vasodilatory pathway described in the Sustained Vasodilatory Responses section may be present in invading trophoblasts.…”

Section: Pathophysiology Of Preeclampsia: Stage Imentioning

confidence: 99%

Emerging Role of Relaxin in the Maternal Adaptations to Normal Pregnancy: Implications for Preeclampsia

Conrad

2011

Seminars in Nephrology

117

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Summary Relaxin is an approximately 6-kilodalton peptide hormone secreted by the corpus luteum, and circulates in the maternal blood during pregnancy. Relaxin administration to awake, chronically instrumented, nonpregnant rats mimics the vasodilatory phenomena of pregnancy. Furthermore, immunoneutralization of relaxin or its elimination from the circulation during midterm pregnancy in awake rats prevents maternal systemic and renal vasodilation, and the increase in global arterial compliance. Human investigation, albeit limited through 2009, also reveals vasodilatory effects of relaxin in the nonpregnant condition and observations consistent with a role for relaxin in gestational hyperfiltration. Recent evidence suggests that the vasodilatory responses of relaxin are mediated by its major receptor, the relaxin/insulin-like family peptide 1 receptor, RFXP1. The molecular mechanisms of relaxin vasodilation depend on the duration of hormone exposure (ie, there are rapid and sustained vasodilatory responses). Newly emerging data support the role of Gai/o protein coupling to phosphatidylinositol-3 kinase/Akt (protein kinase B)-dependent phosphorylation and activation of endothelial nitric oxide synthase in the rapid vasodilatory responses of relaxin. Sustained vasodilatory responses critically depend on vascular endothelial and placental growth factors, and increases in arterial gelatinase(s) activity. Gelatinases hydrolyze big endothelin (ET) at a gly-leu bond to form ET1–32, which activates the endothelial ETB/nitric oxide vasodilatory pathway. Although the relevance of relaxin biology to preeclampsia is largely speculative at this point in time, there are several potential tantalizing links that are discussed in the context of our current understanding of the etiology and pathophysiology of the disease.

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Effects of recombinant H2 relaxin on the expression of matrix metalloproteinases and tissue inhibitor metalloproteinase in cultured early placental extravillous trophoblasts

Cited by 11 publications

References 33 publications

Relaxin in Obstructive Sleep Apnea: Relationship with Blood Pressure and Inflammatory Mediators

Relaxin in Obstructive Sleep Apnea: Relationship with Blood Pressure and Inflammatory Mediators

Progesterone, thyroid hormone and relaxin in the regulation of the invasive potential of extravillous trophoblasts in early placental development

Emerging Role of Relaxin in the Maternal Adaptations to Normal Pregnancy: Implications for Preeclampsia

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