It Takes Two to Tango: Endothelial TGFβ/BMP Signaling Crosstalk with Mechanobiology.
Christian HiepenPaul-Lennard MendezPetra KnausPublished in: Cells (2020)
Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta (TGFβ) 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 TGFβ/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 TGFβ/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 TGFβ/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 TGFβ/BMP growth factor signaling.
Keyphrases
- transforming growth factor
- epithelial mesenchymal transition
- bone regeneration
- endothelial cells
- mesenchymal stem cells
- growth factor
- blood flow
- extracellular matrix
- systematic review
- nitric oxide
- bone mineral density
- bone marrow
- dna damage
- stem cells
- vascular endothelial growth factor
- transcription factor
- signaling pathway
- genome wide
- soft tissue
- cell death
- single cell
- cell therapy
- anti inflammatory
- cell cycle arrest
- cell proliferation
- high glucose
- pi k akt