Distribution of vitamin A-storing lipid droplets in hepatic stellate cells in liver lobules?A comparative study

Abstract Morphological lesions in hepatic stellate cells caused by the immunosuppressive doses of dexamethasone were investigated in dogs. The archival samples of liver collected during a surgical biopsy were examined. The samples were fixed in 10% buffered formalin or Carnoy’s solution and then stained with routine histochemical methods. The lesions were also investigated under electron microscope. It was demonstrated that the number of stellate cells significantly increased (P = 0.0277), yet the size of cytoplasmic lipid droplets significantly decreased (P = 0.0001). Even though steroid-induced hepatopathy is considered to be a reversible pathology, and the lesions in hepatocytes under the influence of dexamethasone occur in a short period, it was found that hepatic stellate cells proliferated and underwent activation. This resulted in collagen accumulation in the hepatic sinuses. The functional and morphological disturbances in the canine liver in the course of steroid-induced hepatopathy are initially subclinical, but the changes in the structure and function of hepatic stellate cells may become a cause of lesions in the wall of hepatic sinusoidal vessels, which may induce additional functional pathologies unrelated to the damage to hepatocytes.

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Identification and Characterization of Vitamin A-Storing Cells in Fetal Liver: Implications for Functional Importance of Hepatic Stellate Cells in Liver Development and Hematopoiesis

Stem Cells ◽

10.1634/stemcells.2006-0316 ◽

2007 ◽

Vol 25 (9) ◽

pp. 2339-2349 ◽

Cited By ~ 46

Author(s):

Hiroshi Kubota ◽

Hsin-lei Yao ◽

Lola M. Reid

Keyword(s):

Vitamin A ◽

Hepatic Stellate Cells ◽

Fetal Liver ◽

Stellate Cells ◽

Liver Development ◽

Functional Importance ◽

Identification And Characterization

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Role of TGF-β signaling in differentiation of mesothelial cells to vitamin A-poor hepatic stellate cells in liver fibrosis

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00257.2015 ◽

2016 ◽

Vol 310 (4) ◽

pp. G262-G272 ◽

Cited By ~ 14

Author(s):

Yuchang Li ◽

Ingrid Lua ◽

Samuel W. French ◽

Kinji Asahina

Keyword(s):

Liver Fibrosis ◽

Vitamin A ◽

Hepatic Stellate Cells ◽

Transforming Growth Factor ◽

Stellate Cells ◽

Mesothelial Cells ◽

Mesenchymal Transition ◽

Duct Ligation ◽

Liver Surface

Mesothelial cells (MCs) form a single layer of the mesothelium and cover the liver surface. A previous study demonstrated that, upon liver injury, MCs migrate inward from the liver surface and give rise to hepatic stellate cells (HSCs) in biliary fibrosis induced by bile duct ligation (BDL) or myofibroblasts in CCl4-induced fibrosis. The present study analyzed the role of transforming growth factor-β (TGF-β) signaling in mesothelial-mesenchymal transition (MMT) and the fate of MCs during liver fibrosis and its regression. Deletion of TGF-β type II receptor ( Tgfbr2) gene in cultured MCs suppressed TGF-β-mediated myofibroblastic conversion. Conditional deletion of Tgfbr2 gene in MCs reduced the differentiation of MCs to HSCs and myofibroblasts in the BDL and CCl4 models, respectively, indicating that the direct TGF-β signaling in MCs is responsible to MMT. After BDL and CCl4 treatment, MC-derived HSCs and myofibroblasts were distributed near the liver surface and the thickness of collagen was increased in Glisson's capsule beneath the liver surface. Fluorescence-activated cell sorting analysis revealed that MC-derived HSCs and myofibroblasts store little vitamin A lipids and have fibrogenic phenotype in the fibrotic livers. MCs contributed to 1.4 and 2.0% of activated HSCs in the BDL and CCl4 models, respectively. During regression of CCl4-induced fibrosis, 20% of MC-derived myofibroblasts survived in the liver and deactivated to vitamin A-poor HSCs. Our data indicate that MCs participate in capsular fibrosis by supplying vitamin A-poor HSCs during a process of liver fibrosis and regression.

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