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Cited by 71Liver physiology and pathologyCellular Mechanics and InteractionsLiver Disease Diagnosis and Treatment

Mechanical homeostasis imbalance in hepatic stellate cells activation and hepatic fibrosis

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Zhao, Yuan-Quan, Deng, Xi-Wen, Xu, Guo-Qi, Lin, Jie, Lu, Hua-Ze, Chen, Jie·2023·Frontiers in Molecular Biosciences
DOI 10.3389/fmolb.2023.1183808PMC PMC10157180
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Abstract

Chronic liver disease or repeated damage to hepatocytes can give rise to hepatic fibrosis. Hepatic fibrosis (HF) is a pathological process of excessive sedimentation of extracellular matrix (ECM) proteins such as collagens, glycoproteins, and proteoglycans (PGs) in the hepatic parenchyma. Changes in the composition of the ECM lead to the stiffness of the matrix that destroys its inherent mechanical homeostasis, and a mechanical homeostasis imbalance activates hepatic stellate cells (HSCs) into myofibroblasts, which can overproliferate and secrete large amounts of ECM proteins. Excessive ECM proteins are gradually deposited in the Disse gap, and matrix regeneration fails, which further leads to changes in ECM components and an increase in stiffness, forming a vicious cycle. These processes promote the occurrence and development of hepatic fibrosis. In this review, the dynamic process of ECM remodeling of HF and the activation of HSCs into mechanotransduction signaling pathways for myofibroblasts to participate in HF are discussed. These mechanotransduction signaling pathways may have potential therapeutic targets for repairing or reversing fibrosis.

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  • Piezo1 channels contribute to liver fibrosis by influencing the mechanosensing functions and biochemical pathways of HSCs.

    “These channels also contribute to liver fibrosis by influencing the mechanosensing functions and biochemical pathways of HSCs.14,43,73”

    From Mechanosensitive calcium ion channels Piezo1: A therapeutic target in liver disease (2025) · cites this paper as [73]

    Section 5.6 (page not provided) links Piezo1-mediated mechanosensing and downstream signaling to liver fibrosis, but the described mechanism occurs in liver sinusoidal endothelial cells, not HSCs. The section also says liver-disease research is limited and describes a broader role for Piezo channels in hepatic fibrosis as possible, so it does not establish the claimed HSC-specific contribution. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • KCs participate in phagocytosis, antigen presentation, as well as the generation of pro-inflammatory and pro-fibrotic cytokines, inducing inflammation, necrosis, regeneration, and fibrosis.

    “KCs participate in phagocytosis, antigen presentation, as well as the generation of pro-inflammatory and pro-fibrotic cytokines, inducing inflammation, necrosis, regeneration, and fibrosis.70,72,73”

    From Mechanosensitive calcium ion channels Piezo1: A therapeutic target in liver disease (2025) · cites this paper as [73]

    Section 4 (page not provided) describes Kupffer cells phagocytosing harmful substances and regulating the liver immune response. It also links hepatic macrophage cytokines to inflammation and fibrosis, but specifically distinguishes Kupffer cells from monocyte-derived macrophages that produce inflammatory cytokines. The copy does not establish the claimed Kupffer-cell role in antigen presentation or the full sequence of inflammation, necrosis, regeneration, and fibrosis. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

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Authors
Zhao, Y.-Q., Deng, X.-W., Xu, G.-Q., Lin, J., Lu, H.-Z., & Chen, J.
Affiliations
Guangxi Medical University (CN)
Corresponding author
Chen, Jie
ORCID
Venue
Frontiers in Molecular Biosciences
Publisher
Frontiers Media SA
Published
2023-04-20
Volume
10
Pages
1183808-1183808
ISSN
2296-889X (ISSN-L)
DOI
10.3389/fmolb.2023.1183808
PMC
PMC10157180
OpenAlex
W4366549268
Cited by
71
References
170
Citations by year
2026: 27 · 2025: 24 · 2024: 15 · 2023: 5
FWCI
3.06
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Molecular Biosciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Natural Science Foundation of China
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
Keywords
liver fibrosis, hepatic stellate cells, mechanical homeostasis, extracellular matrix remodeling, extracellular matrix stiffness, mechanotransduction, myofibroblast activation, chronic liver disease, fibrosis reversal

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