The Role of Mesothelial Cells in Liver Development, Injury, and Regeneration

Mesothelial cells (MCs) cover the surface of visceral organs and the parietal walls of cavities, and they synthesize lubricating fluids to create a slippery surface that facilitates movement between organs without friction. Recent studies have indicated that MCs play active roles in liver development, fibrosis, and regeneration. During liver development, the mesoderm produces MCs that form a single epithelial layer of the mesothelium. MCs exhibit an intermediate phenotype between epithelial cells and mesenchymal cells. Lineage tracing studies have indicated that during liver development, MCs act as mesenchymal progenitor cells that produce hepatic stellate cells, fibroblasts around blood vessels, and smooth muscle cells. Upon liver injury, MCs migrate inward from the liver surface and produce hepatic stellate cells or myofibroblast depending on the etiology, suggesting that MCs are the source of myofibroblasts in capsular fibrosis. Similar to the activation of hepatic stellate cells, transforming growth factor β induces the conversion of MCs into myofibroblasts. Further elucidation of the biological and molecular changes involved in MC activation and fibrogenesis will contribute to the development of novel approaches for the prevention and therapy of liver fibrosis.

Mest Attenuates CCl4-Induced Liver Fibrosis in Rats by Inhibiting the Wnt/beta-Catenin Signaling Pathway

BACKGROUND/AIMS: The Wnt/beta-catenin signaling pathway has been reported to play an important role in liver fibrosis. This study was designed to investigate whether mesoderm-specific transcript homologue (Mest), a strong negative regulator of Wnt/beta-catenin signaling, could inhibit liver fibrosis. METHODS: pcDNA-Mest was transfected into hepatic stellate cells (HSCs) and rats. Rats were randomly divided into four groups: normal group (normal saline), treatment group (pcDNA-Mest+CCl4), control group (pcDNA-neo+CCl4), and model group (normal saline+CCl4). Changes in liver pathology were evaluated by hematoxylin and eosin and Masson's trichrome staining. The levels of alanine transaminase, aspartate transaminase, lactic dehygrogenase, hyaluronic acid, and laminin in the serum and hydroxyproline in the liver were detected by biochemical examination and radioimmunoassay, respectively. The expression and distribution of beta-catenin, alpha-smooth muscle actin (alpha-SMA), Smad3, and tissue inhibitor of metalloproteinase type I were determined, and the viability of the HSCs was tested. RESULTS: Our data demonstrate that Mest alleviated CCl4-induced collagen deposition in liver tissue and improved the condition of the liver in rats. Mest also significantly reduced the expression and distribution of beta-catenin, alpha-SMA and Smad3 both in vivo and in vitro, in addition to the viability of HSCs in vitro. CONCLUSIONS: We found that Mest attenuates liver fibrosis by repressing beta-catenin expression, which provides a new therapeutic approach for treating liver fibrosis.

Impact of hypertension in liver regeneration in rats / Repercussão da hipertensão arterial na regeneração hepática em ratos

PURPOSE: To determine the impact of hypertension in liver regeneration, in rats by examining gain in liver mass and the replication of hepatocytes and stellate cells. METHODS: Forty Wistar rats were allocated into two groups of twenty, the control and experiment group. The experiment group animals were submitted to induction of renovascular hypertension. A week later, all the animals underwent a partial hepatectomy. Measurements were taken after 24 hours and seven days, when ten animals in each group were euthanized. Thus, four subgroups were obtained. The livers were excised and sent for histopathological analysis. RESULTS: The control group had a greater gain in liver mass than the experiment group seven days after partial hepatectomy (p=0.0051). The difference in the activate stellate cell count was not statistically significant following analysis after both 24 hours and seven days (p=1.0). A higher number of dividing hepatocytes was observed in the control group seven days after partial hepatectomy (p=0.0014). CONCLUSION: In rats, hypertension had no direct influence on stellate cell replication, but led to a delay in liver mass gain and were shown to be a reduction factor on hepatocyte replication seven7 days after partial hepatectomy.

OBJETIVO: Determinar o impacto da hipertensão arterial sistêmica na regeneração hepática, em ratos, através da análise do ganho de massa hepática e da replicação dos hepatócitos e das células estreladas. MÉTODOS: Alocaram-se 40 ratos Wistar em dois grupos de 20 animais, os grupos controle e experimento. Os do grupo experimento submeteram-se a indução da hipertensão renovascular. Uma semana após, realizou-se hepatectomia parcial em todos os animais. Colheram-se os dados com 24 horas e sete dias, quando dez animais de cada grupo submeteram-se a eutanásia. Assim, obtiveram-se quatro subgrupos. Os fígados foram retirados e enviados para análise histopatológica. RESULTADOS: O grupo controle apresentou maior ganho de massa hepática do que o grupo experimento sete dias após a hepatectomia parcial (p=0,0051). A diferença na contagem das células estreladas ativadas não foi estatisticamente significante nas análises de 24 horas e de sete dias (p=1,0). Um maior número de hepatócitos em divisão foi observado no grupo controle, sete dias após a hepatectomia parcial (p=0,0014). CONCLUSÃO: Em ratos, a hipertensão não teve influência direta sobre a replicação de células estreladas, mas levou ao atraso no ganho de massa hepática e mostrou ser um fator de redução na replicação de hepatócitos sete dias após a hepatectomia parcial.