The BMP Pathway in Blood Vessel and Lymphatic Vessel Biology

Ponomarev, Ljuba C.; Ksiazkiewicz, Jakub; Staring, Michael W.; Luttun, Aernout; Zwijsen, An

doi:10.3390/ijms22126364

Cited by 10 publications

(3 citation statements)

References 259 publications

(383 reference statements)

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“…This is particularly important under challenging environmental conditions of the vasculature such as hyperglycaemia [161], hypoxia [162], or inflammation [163], which are all known to induce hyperpermeability of the vasculature. BMPRs interact with a number of vascular-specific transmembrane proteins in arterial and venous blood vessels and lymphatics, including VEGFR2 and neuropilins (NRP1/2), reviewed in [164]. Furthermore, BMP-9/-10-BMPR2-ALK1 signalling protects ECs from undergoing EndMT, which involves EC activation and extensive transcriptional reprogramming, and leads to a shift of mature ECs towards a mesenchymal phenotype [119,165,166] (Figure 3).…”

Section: Hereditary Pulmonary Arterial Hypertension and Hipscsmentioning

confidence: 99%

Human iPSCs as Model Systems for BMP-Related Rare Diseases

Sánchez-Duffhues,

Hiepen

2023

Cells

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Disturbances in bone morphogenetic protein (BMP) signalling contribute to onset and development of a number of rare genetic diseases, including Fibrodysplasia ossificans progressiva (FOP), Pulmonary arterial hypertension (PAH), and Hereditary haemorrhagic telangiectasia (HHT). After decades of animal research to build a solid foundation in understanding the underlying molecular mechanisms, the progressive implementation of iPSC-based patient-derived models will improve drug development by addressing drug efficacy, specificity, and toxicity in a complex humanized environment. We will review the current state of literature on iPSC-derived model systems in this field, with special emphasis on the access to patient source material and the complications that may come with it. Given the essential role of BMPs during embryonic development and stem cell differentiation, gain- or loss-of-function mutations in the BMP signalling pathway may compromise iPSC generation, maintenance, and differentiation procedures. This review highlights the need for careful optimization of the protocols used. Finally, we will discuss recent developments towards complex in vitro culture models aiming to resemble specific tissue microenvironments with multi-faceted cellular inputs, such as cell mechanics and ECM together with organoids, organ-on-chip, and microfluidic technologies.

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Section: Hereditary Pulmonary Arterial Hypertension and Hipscsmentioning

confidence: 99%

Human iPSCs as Model Systems for BMP-Related Rare Diseases

Sánchez-Duffhues,

Hiepen

2023

Cells

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“…Furthermore, the cooperation of three di erent vascular systems, the systemic, the pulmonary and the lymphatic circulation, each of which is lined on the inside by a single layer of endothelial cells is essential to keep the body healthy. e role of BMP/ SMAD signaling in lymphatic vessels is poorly known (98). Recent work shows that BMP/SMAD signaling is very regionalized within di erent lymphatic vessels in mice which suggests a role in lymphatic endothelium heterogeneity.…”

Section: Vascular and Cardiovascular Bmp Signallingmentioning

confidence: 99%

State-of-the-art of the Bone Morphogenetic Protein research field: 13th International BMP Conference, Dubrovnik 2022

Štoković¹,

Ivanjko²,

Jelić³

et al. 2022

Rad Hrvatske akademije znanosti i umjetnosti

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who got an insight into the latest achievements in basic, translational, and clinical research of BMP molecules through 75 lectures categorized into several scienti c sections. is review paper provides the most important novel ndings on the structure, function, and signaling of BMPs, the role of BMPs in patterning and organoids as well as the role of BMP in metabolism. Moreover, we discussed the role of BMPs in various diseases including cancer pathogenesis, pulmonary arterial hypertension, and brodysplasia ossi cans progressiva (FOP). Finally, we provided an overview of the new BMP-based therapies in regenerative medicine that are currently in di erent stages of preclinical and clinical trials.

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“…Whereas a similar pathway responds to the different systems in a varied time scale. In contrast, BMP signaling in lymphatic commitment in humans is on the order of hours, so that noise filtering is a more dominant performing objective than response speed [19][20][21][22]. As demonstrated in each of these model systems, the time scale of BMP pathway activation and response, and noise control response to the input signal must be tightly regulated.…”

Section: Introductionmentioning

confidence: 99%

Optimal Performance Objectives in the Highly Conserved Bone Morphogenetic Protein Signaling Pathway

Shaikh,

Larson,

Hanjaya-Putra

et al. 2024

Preprint

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Throughout development, complex networks of cell signaling pathways drive cellular decision-making across different tissues and contexts. The transforming growth factor β (TGF-β) pathways, including the BMP/Smad pathway, play crucial roles in these cellular responses. However, as the Smad pathway is used reiteratively throughout the life cycle of all animals, its systems-level behavior varies from one context to another, despite the pathway connectivity remaining nearly constant. For instance, some cellular systems require a rapid response, while others require high noise filtering. In this paper, we examine how the BMP- Smad pathway balances trade-offs among three such systems-level behaviors, or “Performance Objectives (POs)”: response speed, noise amplification, and the sensitivity of pathway output to receptor input. Using a Smad pathway model fit to human cell data, we show that varying non-conserved parameters (NCPs) such as protein concentrations, the Smad pathway can be tuned to emphasize any of the three POs and that the concentration of nuclear phosphatase has the greatest effect on tuning the POs. However, due to competition among the POs, the pathway cannot simultaneously optimize all three, but at best must balance trade-offs among the POs. We applied the multi-objective optimization concept of the Pareto Front, a widely used concept in economics to identify optimal trade-offs among various requirements. We show that the BMP pathway efficiently balances competing POs across species and is largely Pareto optimal. Our findings reveal that varying the concentration of NCPs allows the Smad signaling pathway to generate a diverse range of POs. This insight identifies how signaling pathways can be optimally tuned for each context.

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The BMP Pathway in Blood Vessel and Lymphatic Vessel Biology

Cited by 10 publications

References 259 publications

Human iPSCs as Model Systems for BMP-Related Rare Diseases

Human iPSCs as Model Systems for BMP-Related Rare Diseases

State-of-the-art of the Bone Morphogenetic Protein research field: 13th International BMP Conference, Dubrovnik 2022

Optimal Performance Objectives in the Highly Conserved Bone Morphogenetic Protein Signaling Pathway

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