It Takes Two to Tango: Endothelial TGFβ/BMP Signaling Crosstalk with Mechanobiology

被引:37
|
作者
Hiepen, Christian [1 ]
Mendez, Paul-Lennard [1 ]
Knaus, Petra [1 ]
机构
[1] Free Univ Berlin, Inst Chem & Biochem, Knaus Lab, Signal Transduct, D-14195 Berlin, Germany
关键词
BMP; TGFβ mechanobiology; endothelial-cell; shear stress; BONE MORPHOGENETIC PROTEIN; GROWTH-FACTOR-BETA; FLUID SHEAR-STRESS; INNER NUCLEAR-MEMBRANE; RECEPTOR-LIKE KINASE-1; NITRIC-OXIDE SYNTHASE; MESENCHYMAL TRANSITION; VE-CADHERIN; GENE-EXPRESSION; TRANSFORMING GROWTH-FACTOR-BETA-1;
D O I
10.3390/cells9091965
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta (TGF beta) superfamily of cytokines. While some ligand members are potent inducers of angiogenesis, others promote vascular homeostasis. However, the precise understanding of the molecular mechanisms underlying these functions is still a growing research field. In bone, the tissue in which BMPs were first discovered, crosstalk of TGF beta/BMP signaling with mechanobiology is well understood. Likewise, the endothelium represents a tissue that is constantly exposed to multiple mechanical triggers, such as wall shear stress, elicited by blood flow or strain, and tension from the surrounding cells and to the extracellular matrix. To integrate mechanical stimuli, the cytoskeleton plays a pivotal role in the transduction of these forces in endothelial cells. Importantly, mechanical forces integrate on several levels of the TGF beta/BMP pathway, such as receptors and SMADs, but also global cell-architecture and nuclear chromatin re-organization. Here, we summarize the current literature on crosstalk mechanisms between biochemical cues elicited by TGF beta/BMP growth factors and mechanical cues, as shear stress or matrix stiffness that collectively orchestrate endothelial function. We focus on the different subcellular compartments in which the forces are sensed and integrated into the TGF beta/BMP growth factor signaling.
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页数:33
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