Transforming Growth Factor <i>β</i>1 Increases Expression of Contractile Genes in Human Pulmonary Arterial Smooth Muscle Cells by Potentiating Sphingosine-1-Phosphate Signaling

Ji, Yajing; Lisabeth, Erika M.; Neubig, Richard R.

doi:10.1124/molpharm.120.000019

Cited by 7 publications

(2 citation statements)

References 53 publications

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“…IL-6 released by macrophages promotes Matrix metalloproteinase-1 (MMP-1) production by SMC [147]. Other factors such as TGF-β1 that is secreted by the M2 macrophage induces a contractile SMC phenotype [148,149].…”

Section: The Role Of Inflammation In Smc Phenotypic Changementioning

confidence: 99%

Role of Vascular Smooth Muscle Cell Phenotype Switching in Arteriogenesis

Ashraf

Zen

2021

IJMS

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Arteriogenesis is one of the primary physiological means by which the circulatory collateral system restores blood flow after significant arterial occlusion in peripheral arterial disease patients. Vascular smooth muscle cells (VSMCs) are the predominant cell type in collateral arteries and respond to altered blood flow and inflammatory conditions after an arterial occlusion by switching their phenotype between quiescent contractile and proliferative synthetic states. Maintaining the contractile state of VSMC is required for collateral vascular function to regulate blood vessel tone and blood flow during arteriogenesis, whereas synthetic SMCs are crucial in the growth and remodeling of the collateral media layer to establish more stable conduit arteries. Timely VSMC phenotype switching requires a set of coordinated actions of molecular and cellular mediators to result in an expansive remodeling of collaterals that restores the blood flow effectively into downstream ischemic tissues. This review overviews the role of VSMC phenotypic switching in the physiological arteriogenesis process and how the VSMC phenotype is affected by the primary triggers of arteriogenesis such as blood flow hemodynamic forces and inflammation. Better understanding the role of VSMC phenotype switching during arteriogenesis can identify novel therapeutic strategies to enhance revascularization in peripheral arterial disease.

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Section: The Role Of Inflammation In Smc Phenotypic Changementioning

confidence: 99%

Role of Vascular Smooth Muscle Cell Phenotype Switching in Arteriogenesis

Ashraf

Zen

2021

IJMS

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“…As mentioned, PF-543 has not been tested in trophoblasts or in placental explants previously. Nonetheless, 1 μM [ 72 , 73 ] and even 10 μM [ 74 ] of PF-543 is a commonly used concentration in a monolayer culture of cells isolated from other tissues.…”

Section: Discussionmentioning

confidence: 99%

Tumor Necrosis Factor-α Induces a Preeclamptic-like Phenotype in Placental Villi via Sphingosine Kinase 1 Activation

Fakhr

Koshti

Habibyan

et al. 2022

IJMS

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Preeclampsia (PE) involves inadequate placental function. This can occur due to elevated pro-inflammatory tumor necrosis factor-α (TNF-α). In other tissues, TNF-α signals via sphingosine kinase 1 (SphK1). SphK1 hinders syncytial formation. Whether this occurs downstream of TNF-α signaling is unclear. We hypothesized that placental SphK1 levels are higher in PE and elevated TNF-α decreases syncytial function, increases syncytial shedding, and increases cytokine/factor release via SphK1 activity. Term placental biopsies were analyzed for SphK1 using immunofluorescence and qRT-PCR. Term placental explants were treated after 4 days of culture, at the start of syncytial regeneration, with TNF-α and/or SphK1 inhibitors, PF-543. Syncytialization was assessed by measuring fusion and chorionic gonadotropin release. Cell death and shedding were measured by lactate dehydrogenase release and placental alkaline phosphatase-positive shed particles. Forty-two cytokines were measured using multiplex assays. Placental SphK1 was increased in PE. Increased cell death, shedding, interferon-α2, IFN-γ-induced protein 10, fibroblast growth factor 2, and platelet-derived growth factor-AA release induced by TNF-α were reversed upon SphK1 inhibition. TNF-α increased the release of 26 cytokines independently of SphK1. TNF-α decreased IL-10 release and inhibiting SphK1 reversed this effect. Inhibiting SphK1 alone decreased TNF-α release. Hence, SphK1 partially mediates the TNF-α-induced PE placental phenotype, primarily through cell damage, shedding, and specific cytokine release.

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