hole liver only flows towards the remaining 1/3 with the liver tissue (36). A uncomplicated mathematical deduction demonstrates that this will likely inevitably lead to two results: initially, the friction exerted by blood flow on the endothelial surface increases substantially, that is certainly, there is a rise in shear strain (37,38); second, every liver cell getting a number of signal elements from the portal vein is quite a few times that just before liver resection. The hepatic-portal shunt model was established to help keep the blood pressure constant and steady after PHx. Prior findings indicate that the liver could not regenerate in time, which confirm the critical part of portal blood pressure alterations for liver injury perception and growth signal activation (39). Research have discovered that FGFR4 custom synthesis hemodynamic changes within the portal vein lead to elevated shear anxiety in liver sinusoidal endothelial cells (LSECs), which in turn promotes the release of nitric oxide (NO), which increases the sensitivity of hepatocytes to hepatocyte growth element (HGF) (40), induces vascular endothelial development 5-HT1 Receptor drug factor (VEGF) (41,42), and stimulates HSCs to release HGF and VEGF (43). The interleukin (IL)-6 released by LSEC could also result in a rise in shear stress. Compared with unstretched LSECs, mechanically stretched LSECs releases extra IL-6 (44). Correspondingly, an improvement in shear anxiety will boost the activity of urokinase-type plasminogen activator (uPA) (45,46). The rapid activation of uPA causes the conversion of plasminogen to plasmin, which subsequently initiates breakdown of extracellular matrix (ECM) constituents and cuts precursor (pro-HGF) molecules into active HGF binding to hepatocyte growth element receptor (HGFR or c-Met) (47-50). EGF increases in relative concentration as a result of enhance in portal venous flow and motivates the epidermal growth factor receptor (EGFR, also known as ErbB) (51,52). Activated HGFR and EGFR trigger the liver regeneration cascade, including phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinases (MAPK, also known as Ras/Raf/MEK/Erk), and elevate the enhanced expression of c-myc, c-fos, c-jun, and also other transcription factors, which finally facilitates protein synthesis and cell division (40). Innate immune response The innate immune response is also regarded as a major stimulus of liver regeneration (53,54). As elements of innate immunity, lipopolysaccharide (LPS) and complements (like C3a and C5a) are released from the intestinal tractAnn Transl Med 2021;9(22):1705 | dx.doi.org/10.21037/atm-21-Annals of Translational Medicine, Vol 9, No 22 November 2021 Table 1 The potential mechanisms through which PHx could trigger liver regeneration Trigger Elevation of shear stress Elevation of shear pressure Elevation of shear anxiety Elevation of shear tension Innate immune response Innate immune response Innate immune response Hemostasis activation Hemostasis activation Animal Rat Rat Mice Degree of PHx Effect MechanismPage 5 ofRef (38) (40) (42)2/3PHx Initiates and maintains liver regeneration 2/3PHx Triggers the liver regeneration cascade 2/3PHx The decreased serum nitrate and nitrite levels lead to lower liver mass recovery and higher ALT 2/3PHx Initiates liver regenerationProper portal blood perfusion; Hepatocyte membrane and sodium-potassium pump adjustments Expression of c-fos mRNA; Release of NO and proliferation elements Release of NO; The HSP70 family and Ki-67; Induction of Nrp1 and EGFR uPA and uPAR activat
