Inhibition of the JAK2/STAT3/SOSC1 Signaling Pathway Improves Secretion Function of Vascular Endothelial Cells in a Rat Model of Pregnancy-Induced Hypertension

Luo, Jun; Fu, Dan; Wu, Yaqin; Gao, Ying

doi:10.1159/000452566

Cited by 18 publications

(20 citation statements)

References 42 publications

(45 reference statements)

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“…STAT3 activation is involved in regulating essential cellular functions including cell motility, a key cellular activity required for proper placental development, in many cell types [17]. Placental development requires a precise coordination of cellular proliferation, differentiation and migration, and importantly the invasion of trophoblast cells into the endometrium to establish a fetal blood supply.…”

Section: Introductionmentioning

confidence: 99%

Suppression of STAT3 Signaling by Δ9-Tetrahydrocannabinol (THC) Induces Trophoblast Dysfunction

Chang¹,

Bian²,

He³

et al. 2017

Cell Physiol Biochem

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Aims: Marijuana is a widely used illicit drug and its consumption during pregnancy has been associated with adverse reproductive outcomes. The purpose of this study was to determine the effects of chronic intake of Δ⁹-tetrahydrocannabinol (THC), the major component of marijuana, on trophoblast function, placental development, and birth outcomes. Methods: The pathological characteristics and distribution of cannabinoid receptors in placenta were observed by immunohistochemical (IHC) staining. Cell migration in response to THC was measured by transwell assays. The levels of cannabinoid receptors and Signal Transducer and Activator of Transcription 3 (STAT3) were detected by western blot. Results: We found the placenta expressed two main cannabinoid receptors, suggesting that THC induced biological responses in placental cells. Supporting this hypothesis, we observed dramatic alterations of placental morphology in marijuana users. Using THC and inhibitors of cannabinoid receptors, we demonstrated that THC impaired trophoblast cell migration and invasion partly via cannabinoid receptors. Additionally, pregnant mice injected with THC showed adverse reproductive events including reduced number of fetuses, lower maternal and placental weights. Mechanistically, STAT3 signaling pathway was involved in the THC-induced suppression of trophoblast cell motility and pregnancy outcomes. Conclusion: Our study indicates that the STAT3 signaling pathway plays a critical role in THC-induced trophoblast dysfunction.

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Section: Introductionmentioning

confidence: 99%

Suppression of STAT3 Signaling by Δ9-Tetrahydrocannabinol (THC) Induces Trophoblast Dysfunction

Chang¹,

Bian²,

He³

et al. 2017

Cell Physiol Biochem

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“…We found thatthe expression levels of the JAK2/STAT3 signaling pathway were also significantly inhibited or activated. Similarly, it has been reported that the abnormal expression of IL-6, IL-10 and TNF-α may lead to the activation of the JAK/STAT pathway 31 . Previous studies have also demonstrated the inhibition by AG490 on the growth of malignant cells from patients with acute lymphocytic leukemia (ALL) and mycosis fungoides (MF) 30 .…”

Section: Discussionmentioning

confidence: 88%

“…It has been demonstrated that autocrine IL-6 production can induce the constitutive activation of STAT3, which plays a major role in STAT proteins in oncogenesis 30 . However, AG490 can effectively block the activation of the JAK2/STAT3 signaling pathway in different cancer cell lines 28 , 31 . In this study, to determine the correlation between MLAA-34 and JAK2/STAT3 pathway, an inhibitor of JAK2 (AG490) or an activator of JAK2 (IL-6) were treated in U937 cells.…”

Section: Discussionmentioning

confidence: 99%

MLAA-34 knockdown shows enhanced antitumor activity via JAK2/STAT3 signaling pathway in acute monocytic leukemia

et al. 2020

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MLAA-34 is a novel leukemia-associated gene closely related to the carcinogenesis of acute monocytic leukemia (AML). MLAA-34 over expression has been observed to inhibit apoptosis in vitro . JAK2/STAT3 pathway plays an important role in cell proliferation, differentiation and inhibition of apoptosis in number of cancers. However, the relationship and interaction between MLAA-34 and JAK2/STAT3 has never been investigated in AML. This study investigates and reports a novel relationship between MLAA-34 and JAK2/STAT3 pathway in AML both in vitro and in vivo . We constructed MLAA-34 knockdown vector and transfected U937 cells to observe its apoptotic activities in relation to JAK2/STAT3 signaling pathway in vitro and then in vivo in mouse model. Levels of expression of MLAA-34 and JAK2/STAT3 and its downstream targets were also measured in AML patients and a few volunteers. We found that MLAA-34 knockdown increased U937 apoptosis in vitro and inhibited tumor growth in vivo . Components of the canonical JAK2/STAT3 pathway or its downstream targets, including c-myc, bcl-2, Bax, and caspase-3, were shown to be involved in the carcinogenesis of AML. We also found that the JAK2/STAT3 pathway positively regulated MLAA-34 expression. We additionally identified a STAT3 binding site in the MLAA-34 promoter where STAT3 binds directly and activates MLAA-34 expression. In addition, MLAA-34 was found to form a complex with JAK2 and was enhanced by JAK2 activation. Correlation of MLAA-34 and JAK2/STAT3 was further confirmed in AML patients. In conclusion, MLAA-34 is a novel regulator for JAK2/STAT3 signaling, and in turn, is regulated by this interaction in a positive feedback loop. Thus we report a novel model of interaction mechanism between MLAA-34 and JAK2/STAT3 which can be utilized as a potential target for a novel therapeutic approach in AML.

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“…Pregnancy-induced hypertension (PIH) is considered a major cause of perinatal and maternal mortality, including gestational hypertension (GH) and preeclampsia (PE) [1]. However, the underlying mechanism of PIH remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Honokiol inhibits inflammation and endoplasmic reticulum stress in a rat model of pregnancy-induced hypertension

Wei

Liu

Ying

et al. 2020

Biotechnology & Biotechnological Equipment

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The levels of inflammatory factors in pregnancy-induced hypertension (PIH) are closely correlated with the severity of the disease. The enhanced endoplasmic reticulum (ER) stress response and upregulated iNOS might contribute to the pathophysiology of preeclampsia. Honokiol has been shown to be a potential anti-inflammatory and anti-ER stress agent. However, the effect of honokiol on the inflammation and ER stress has not been investigated in a gestational hypertensive model. The present study aimed to elucidate the role of honokiol in inflammation, ER stress and endothelial/inducible nitric oxide synthase (eNOS/iNOS) in a PIH rat model. Rats with hypoxia-induced PIH were administered honokiol (0, 200, 600, 2000 lg/kg) daily for one week to different groups by intragastric administration. Systolic blood pressure (SBP) and urinary protein concentration were measured via the tail-cuff method and CBB kit. Proinflammatory cytokines and ER-stress markers, VEGF, NO, iNOS and eNOS in the plasma or placental tissue were analyzed by enzyme-linked immunosorbent assay (ELISA), quantitative real time polymerase chain reaction (RT-qPCR), NO assay kit or western blot. The blood pressure and urinary protein level in PIH rats were significantly decreased after honokiol. Honokiol significantly inhibited the elevated levels of proinflammatory cytokines and ER-stress markers, which were accompanied by the upregulation of eNOS, NO and VEGF mRNA in PIH rats. However, the level of iNOS was reduced by honokiol. Our study suggests a beneficial potential of honokiol in PIH rats through inhibition of proinflammatory cytokines and ER stress. Honokiol could be an intriguing therapeutic approach in ER stress related PIH.

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Inhibition of the JAK2/STAT3/SOSC1 Signaling Pathway Improves Secretion Function of Vascular Endothelial Cells in a Rat Model of Pregnancy-Induced Hypertension

Cited by 18 publications

References 42 publications

Suppression of STAT3 Signaling by Δ9-Tetrahydrocannabinol (THC) Induces Trophoblast Dysfunction

Suppression of STAT3 Signaling by Δ9-Tetrahydrocannabinol (THC) Induces Trophoblast Dysfunction

MLAA-34 knockdown shows enhanced antitumor activity via JAK2/STAT3 signaling pathway in acute monocytic leukemia

Honokiol inhibits inflammation and endoplasmic reticulum stress in a rat model of pregnancy-induced hypertension

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