Multiscale biomechanics and mechanotransduction from liver fibrosis to cancer

Li, Ning; Zhang, Xiaoyu; Zhou, Jin; Li, Wang; Shu, Xinyu; Wu, Yi; Long, Mian

doi:10.1016/j.addr.2022.114448

Cited by 39 publications

(21 citation statements)

References 270 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Calculations from liver elastography in an experimental model of diet-induced fatty liver have demonstrated that hepatocellular ballooning and inflammation are associated with an approximately 20% reduction of the sinusoidal diameter, representing a significant loss of vascular space [58,60] . As such, these viscoelasticity assessments appear consistent with earlier architectural and hemodynamic observations about the effect of steatosis on liver microcirculation, describing tortuous and narrowed channels and impaired sinusoidal flow in experimentally induced fatty liver and human fatty liver [48,49,61,62] . Despite major methodical advances, significant challenges remain in characterizing physiological and pathological changes in blood flow and pressure at the sinusoidal scale [63] .…”

Section: Sinusoidal Biomechanics In Steatosis and Steatohepatitissupporting

confidence: 87%

Mechanobiology in the development and progression of non-alcoholic fatty liver disease: an updated review

Mitten¹,

Baffy²

2023

Metab Target Organ Damage

View full text Add to dashboard Cite

Mechanobiology is a rapidly emerging field focused on the biological impact of physical forces at the molecular, cellular, and tissue level. Living cells perceive mechanical cues and transform them into biochemical signals through mechanotransduction. Mechanotransduction is a complex process that involves mechanosensors (which are located in the plasma membrane or within the cell) and mechanotransmission to the nucleus (which occurs either by physical connection between the mechanosensor and the nucleus or by mechanosignaling through biochemical pathways). Essential biological functions, including development, growth, motility, and metabolism, depend on the mechanoresponses generated by these events. Multiple lines of evidence indicate that disruption of mechanical homeostasis may contribute to the pathogenesis of non-alcoholic fatty liver disease (NAFLD), a highly prevalent metabolic disorder characterized by abnormal accumulation of lipid droplets in hepatocytes (steatosis) and often associated with inflammation and liver cell injury (steatohepatitis). While predicting individual predisposition to adverse outcomes in NAFLD remains a challenge, there is increasing evidence that steatosis and steatohepatitis trigger mechanoresponses that contribute to the early stages of pathogenesis in NAFLD and critically impact disease progression. Lipid accumulation and lipotoxicity modify liver viscoelasticity, alter the biomechanics of liver sinusoids, and initiate aberrant pathways of mechanotransduction in hepatocytes and non-parenchymal liver cells, such as sinusoidal endothelial cells and hepatic stellate cells. Interactions of these cells at mechanical interfaces with each other, with extracellular matrix, and with sinusoidal blood flow are profoundly altered by steatosis and steatohepatitis; such changes may promote a pro-angiogenic and pro-fibrotic milieu. A better understanding of liver mechanobiology may facilitate the identification of novel molecular and cellular targets in the management of NAFLD.

show abstract

Section: Sinusoidal Biomechanics In Steatosis and Steatohepatitissupporting

confidence: 87%

Mechanobiology in the development and progression of non-alcoholic fatty liver disease: an updated review

Mitten¹,

Baffy²

2023

Metab Target Organ Damage

View full text Add to dashboard Cite

show abstract

“…The integrin protein mediates the adhesion between cells and ECM. After being affected by mechanical forces, integrin binds to its ligands and mediates FAK, PI3K, AKT/PKB, and other signaling pathways that regulate cell proliferation, migration, and epithelial-mesenchymal transition [ 67 , 68 ]. By upregulating integrin-β1, the invasion of human trophoblasts can be promoted [ 69 ].…”

Section: Discussionmentioning

confidence: 99%

Stiff Extracellular Matrix Promotes Invasive Behaviors of Trophoblast Cells

Cao

Tang

et al. 2023

Bioengineering

View full text Add to dashboard Cite

The effect of extracellular matrix (ECM) stiffness on embryonic trophoblast cells invasion during mammalian embryo implantation remains largely unknown. In this study, we investigated the effects of ECM stiffness on various aspects of human trophoblast cell behaviors during cell–ECM interactions. The mechanical microenvironment of the uterus was simulated by fabricating polyacrylamide (PA) hydrogels with different levels of stiffness. The human choriocarcinoma (JAR) cell lineage was used as the trophoblast model. We found that the spreading area of JAR cells, the formation of focal adhesions, and the polymerization of the F-actin cytoskeleton were all facilitated with increased ECM stiffness. Significantly, JAR cells also exhibited durotactic behavior on ECM with a gradient stiffness. Meanwhile, stiffness of the ECM affects the invasion of multicellular JAR spheroids. These results demonstrated that human trophoblast cells are mechanically sensitive, while the mechanical properties of the uterine microenvironment could play an important role in the implantation process.

show abstract

“…Hepatocellular carcinoma (HCC) is a tumor that develops after the accumulation of metabolic and inflammatory damage over a long period. Inflammatory cell infiltration, HSC activation, and fibrotic proliferation have been recognized as powerful factors driving HCC progression [ 51 ]. Compared with normal liver tissue, ACSL4 expression was significantly upregulated in HCC tissue, suggesting that ferroptosis may be responsible for the development of HCC [ 52 ].…”

Section: Ferroptosis and Fibrosismentioning

confidence: 99%

Physiological Effects of Ferroptosis on Organ Fibrosis

Dong²,

et al. 2022

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Ferroptosis is a new type of programmed cell death with unique morphological, biochemical, and genetic features. From the initial study of histomorphology to the exploration of subcellular organelles and even molecular mechanisms, a net connecting ferroptosis and fibrosis is being woven and formed. Inflammation may be the bridge between both processes. In this review, we will discuss the ferroptosis theory and process and the physiological functions of ferroptosis, followed by a description of the pathological effects and the underlying mechanisms of ferroptosis in the pathogenesis of tumorigenesis, ischemic damage, degenerative lesions, autoimmune diseases, and necroinflammation. We then focus on the role of ferroptosis in the fibrosis process in the liver, lung, kidney, heart, and other organs. Although the molecular mechanism of ferroptosis has been explored extensively in the past few years, many challenges remain to be resolved to translate this information into antifibrotic practice, which is becoming a promising new direction in the field of fibrotic disease prevention and treatment.

show abstract

Multiscale biomechanics and mechanotransduction from liver fibrosis to cancer

Cited by 39 publications

References 270 publications

Mechanobiology in the development and progression of non-alcoholic fatty liver disease: an updated review

Mechanobiology in the development and progression of non-alcoholic fatty liver disease: an updated review

Stiff Extracellular Matrix Promotes Invasive Behaviors of Trophoblast Cells

Physiological Effects of Ferroptosis on Organ Fibrosis

Contact Info

Product

Resources

About