SMAD6 transduces endothelial cell flow responses required for blood vessel homeostasis

Ruter, Dana L.; Liu, Ziqing; Ngo, Kimlynn M; Shaka, X; Marvin, Allison; Buglak, Danielle B; Kidder, Elise J.; Bautch, Victoria L.

doi:10.1007/s10456-021-09777-7

Cited by 25 publications

(54 citation statements)

References 59 publications

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“…Recently, an additional role of SMAD6 in endothelial cell homeostasis was reported using different human endothelial cell cultures. This work showed that SMAD6 is required when vessels transition from an angiocrine state to a homeostatic maintenance state as a transducer of endothelial cell flow-mediated responsesdownstream of the mechanosensory Notch1 [124]. These different effects of SMAD6 might contribute to the distinct context-dependent functions of BMP signaling in angiogenesis.…”

Section: Inhibitory Smads (I-smads)mentioning

confidence: 86%

“…For instance, BMP4 is strongly downregulated in laminar shear stress conditions in vascular endothelial cells, whereas it is induced under disturbed flow conditions [123]. Moreover, recently, it has been shown that Notch1-mediated upregulation of SMAD6 is necessary for flow-mediated alignment, homeostatic quiescence and the barrier function of blood endothelial cells [124].…”

Section: Mechano-transductionmentioning

confidence: 99%

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The BMP Pathway in Blood Vessel and Lymphatic Vessel Biology

Ponomarev

Ksiazkiewicz

Staring

et al. 2021

IJMS

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Bone morphogenetic proteins (BMPs) were originally identified as the active components in bone extracts that can induce ectopic bone formation. In recent decades, their key role has broadly expanded beyond bone physiology and pathology. Nowadays, the BMP pathway is considered an important player in vascular signaling. Indeed, mutations in genes encoding different components of the BMP pathway cause various severe vascular diseases. Their signaling contributes to the morphological, functional and molecular heterogeneity among endothelial cells in different vessel types such as arteries, veins, lymphatic vessels and capillaries within different organs. The BMP pathway is a remarkably fine-tuned pathway. As a result, its signaling output in the vessel wall critically depends on the cellular context, which includes flow hemodynamics, interplay with other vascular signaling cascades and the interaction of endothelial cells with peri-endothelial cells and the surrounding matrix. In this review, the emerging role of BMP signaling in lymphatic vessel biology will be highlighted within the framework of BMP signaling in the circulatory vasculature.

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Section: Inhibitory Smads (I-smads)mentioning

confidence: 86%

Section: Mechano-transductionmentioning

confidence: 99%

The BMP Pathway in Blood Vessel and Lymphatic Vessel Biology

Ponomarev

Ksiazkiewicz

Staring

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…BMP signaling through SMAD1/5 upregulates expression of SMAD6 and SMAD7, which creates a negative feedback loop for the BMP signaling pathway [ 108 ]. SMAD6 expression is also upregulated by Notch signaling in endothelial cells [ 109 , 110 ]. SMAD6 and SMAD7 can regulate BMP signaling in several ways.…”

Section: Chapter 1: Bmp Signaling In Blood Vessels—the Playersmentioning

confidence: 99%

The versatility and paradox of BMP signaling in endothelial cell behaviors and blood vessel function

Kulikauskas

Shaka

Bautch

2022

Cell. Mol. Life Sci.

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Blood vessels expand via sprouting angiogenesis, and this process involves numerous endothelial cell behaviors, such as collective migration, proliferation, cell–cell junction rearrangements, and anastomosis and lumen formation. Subsequently, blood vessels remodel to form a hierarchical network that circulates blood and delivers oxygen and nutrients to tissue. During this time, endothelial cells become quiescent and form a barrier between blood and tissues that regulates transport of liquids and solutes. Bone morphogenetic protein (BMP) signaling regulates both proangiogenic and homeostatic endothelial cell behaviors as blood vessels form and mature. Almost 30 years ago, human pedigrees linked BMP signaling to diseases associated with blood vessel hemorrhage and shunts, and recent work greatly expanded our knowledge of the players and the effects of vascular BMP signaling. Despite these gains, there remain paradoxes and questions, especially with respect to how and where the different and opposing BMP signaling outputs are regulated. This review examines endothelial cell BMP signaling in vitro and in vivo and discusses the paradox of BMP signals that both destabilize and stabilize endothelial cell behaviors.

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“…Fig. 2H), that functions downstream of NOTCH-signaling to downregulate proliferation and induce junction-associated genes (Ruter et al, 2021).…”

Section: Supplementary Notementioning

confidence: 99%

Developmental origins of cell heterogeneity in the human lung

Sountoulidis

Salas

Braun

et al. 2022

Preprint

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The lung contains numerous specialized cell-types with distinct roles in tissue function and integrity. To clarify the origins and mechanisms generating cell heterogeneity, we created a first comprehensive topographic atlas of early human lung development. We report 83 cell states, several spatially-resolved developmental trajectories and predict cell interactions within defined tissue niches. We integrated scRNA-Seq and spatial transcriptomics into a web-based, open platform for interactive exploration. To illustrate the utility of our approach we show distinct states of secretory and neuroendocrine cells, largely overlapping with the programs activated either during lung fibrosis or small cell lung cancer progression. We define the origin of uncharacterized airway fibroblasts associated with airway smooth muscle in bronchovascular bundles, and describe a trajectory of Schwann cell progenitors to intrinsic parasympathetic neurons controlling bronchoconstriction. Our atlas provides a rich resource for further research and a reference for defining deviations from homeostatic and repair mechanisms leading to pulmonary diseases.

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SMAD6 transduces endothelial cell flow responses required for blood vessel homeostasis

Cited by 25 publications

References 59 publications

The BMP Pathway in Blood Vessel and Lymphatic Vessel Biology

The BMP Pathway in Blood Vessel and Lymphatic Vessel Biology

The versatility and paradox of BMP signaling in endothelial cell behaviors and blood vessel function

Developmental origins of cell heterogeneity in the human lung

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