Abstract
Organogenesis and regeneration are fundamental for developmental progress and are associated with morphogenesis, size control and functional properties for whole-body homeostasis. The liver plays an essential role in maintaining homeostasis of the entire body through various functions, including metabolic functions, detoxification, and production of bile, via the three-dimensional spatial arrangement of hepatic lobules and has high regenerative capacity. The regeneration occurs as hypertrophy, which strictly controls the size and lobule structure. In this study, we established a three-dimensional sinusoidal network analysis method and determined valuable parameters after partial hepatectomy by comparison to the static phase of the liver. We found that mechanical homeostasis, which is crucial for organ morphogenesis and functions in various phenomena, plays essential roles in liver regeneration for both initiation and termination of liver regeneration, which is regulated by cytokine networks. Mechanical homeostasis plays critical roles in the initiation and termination of organogenesis, tissue repair and organ regeneration in coordination with cytokine networks.
Highlights
Organogenesis and regeneration are fundamental for developmental progress and are associated with morphogenesis, size control and functional properties for whole-body homeostasis
The liver is divided into five lobes, i.e., the left lobe (LL), left median lobe (LML), right median lobe (RML), right lobe (RL), and caudate lobe (CL)
In our current study, mechanical homeostasis indicated by fluctuation parameters, including tension and shear stress on liver sinusoidal networks, plays an essential roles in the initiation of liver regeneration
Summary
Organogenesis and regeneration are fundamental for developmental progress and are associated with morphogenesis, size control and functional properties for whole-body homeostasis. Endothelial cells have several receptors, including P2X4 and Piezo[1], as physical force sensors for vascular development and diacylglycerol-sensitive canonical transient receptor potential (TRPC) subunits for sensing membrane stretching, along with G protein-coupled receptors (GPCRs) for sensing these mechanical stresses[20,21,22] Based on these observations, it is hypothesized that mechanical sensors of blood vessels in the liver would have key roles as the triggering and termination signals associated with the successive cytokine networks during liver regeneration. The production of TGFβ1, which is known to inhibit hepatocyte proliferation, was regulated by haemodynamics in the early liver regeneration process These results indicated that mechanical homeostatic signalling, including shear stress and tension, to sinusoidal endothelial cells prior to HGF production plays essential roles in the initiation and termination of liver organ regeneration
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