Regeneration and activation of liver progenitor cells in liver cirrhosis

Yin, Yanze; Kong, Defu; He, Kun; Xia, Qiang

doi:10.1016/j.gendis.2020.07.016

Cited by 5 publications

(6 citation statements)

References 35 publications

(42 reference statements)

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“…HS promote the proliferation of progenitor cells through the secretion of IL-6, fibroblast growth factor 7 (FGF-7), lymphotoxin-beta, and Hh, as reviewed in ref. 87 . HS have also been shown to become progenitor cells and support liver regeneration in a Hedgehog-regulated fashion after hepatectomy 88 .…”

Section: Organ-specific Fibroblasts: Surface Markers and Regenerative Signalsmentioning

confidence: 99%

The bright side of fibroblasts: molecular signature and regenerative cues in major organs

2021

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Fibrosis is a pathologic process characterized by the replacement of parenchymal tissue by large amounts of extracellular matrix, which may lead to organ dysfunction and even death. Fibroblasts are classically associated to fibrosis and tissue repair, and seldom to regeneration. However, accumulating evidence supports a pro-regenerative role of fibroblasts in different organs. While some organs rely on fibroblasts for maintaining stem cell niches, others depend on fibroblast activity, particularly on secreted molecules that promote cell adhesion, migration, and proliferation, to guide the regenerative process. Herein we provide an up-to-date overview of fibroblast-derived regenerative signaling across different organs and discuss how this capacity may become compromised with aging. We further introduce a new paradigm for regenerative therapies based on reverting adult fibroblasts to a fetal/neonatal-like phenotype.

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Section: Organ-specific Fibroblasts: Surface Markers and Regenerative Signalsmentioning

confidence: 99%

The bright side of fibroblasts: molecular signature and regenerative cues in major organs

2021

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“…Main CT findings of these lesions allow making a differential diagnosis with HCC: Regenerative nodules are isodense to liver parenchyma with absent wash-in during the arterial phase. The presence of surrounding fibrosis can be evaluated during the portal phase [ 83 ]. Arterioportal shunts (APSs) are abnormal communications between a hepatic arterial branch and the corresponding portal vein, sinusoid, or peri-biliary venule, causing focal arterialization of liver parenchyma.…”

Section: Ct Findingsmentioning

confidence: 99%

“…Regenerative nodules are isodense to liver parenchyma with absent wash-in during the arterial phase. The presence of surrounding fibrosis can be evaluated during the portal phase [ 83 ].…”

Section: Ct Findingsmentioning

confidence: 99%

Spontaneously Ruptured Hepatocellular Carcinoma: Computed Tomography-Based Assessment

et al. 2023

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Spontaneously ruptured hepatocellular carcinoma (SRHCC) is an uncommon and life-threatening complication in patients with hepatocellular carcinoma (HCC). It is usually associated with chronic liver disease and has a poor prognosis with a high mortality rate during the acute phase. SRHCC can cause a severe and urgent condition of acute abdomen disease and requires a correct diagnosis to achieve adequate treatment. Clinical presentation is related to the presence of hemoperitoneum, and abdominal pain is the most common symptom (66–100% of cases). Although the treatment approach is not unique, trans-arterial (chemo)embolization (TAE/TACE) followed by staged hepatectomy has shown better results in long-term survival. A multi-phase contrast-enhanced CT (CECT) scan is a pivotal technique in the diagnosis of SRHCC due to its diagnostic accuracy and optimal temporal resolution. The correct interpretation of the main CT findings in SRHCC, such as active contrast extravasation and the sentinel clot sign, is fundamental for a prompt and correct diagnosis. Furthermore, CT also plays a role as a post-operative control procedure, especially in patients treated with TAE/TACE. Therefore, a multi-phase CECT scan should be the diagnostic tool of choice in SRHCC since it suggests an immediate need for treatment with a consequent improvement in prognosis.

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“…Surgical removal and other factors of acute or chronic liver injury can lead to liver regeneration. 1 Liver regeneration studies are of great clinical interest, because liver dysfunction after hepatectomy and liver transplantation, especially in patients with cirrhosis and chronic liver failure, depends on the status of liver regeneration. 2 However, liver regeneration is a complex process regulated by a variety of cells, cytokines and biological pathways, 3 and its mechanism is still unclear.…”

Section: Introductionmentioning

confidence: 99%

“…The liver is an important organ of the human body with strong regenerative ability. Surgical removal and other factors of acute or chronic liver injury can lead to liver regeneration 1 . Liver regeneration studies are of great clinical interest, because liver dysfunction after hepatectomy and liver transplantation, especially in patients with cirrhosis and chronic liver failure, depends on the status of liver regeneration 2 .…”

Section: Introductionmentioning

confidence: 99%

Aurora kinase A regulates liver regeneration through macrophages polarization and Wnt/β‐catenin signalling

Yin

Kong

et al. 2021

Liver International

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Background and Aims: Liver regeneration is a complex process regulated by a variety of cells, cytokines and biological pathways. Aurora kinase A (AURKA) is a serine/ threonine kinase that plays a role in centrosome maturation and spindle formation during the cell division cycle. The purpose of this study was to further explore the mechanism of AURKA on liver regeneration and to identify new possible targets for liver regeneration. Methods:The effect and mechanism of AURKA on liver regeneration were studied using a 70% hepatectomy model. Human liver organoids were used as an in vitro model to investigate the effect of AURKA on hepatocyte proliferation.Results: AURKA inhibition significantly reduced the level of β-catenin protein by reducing the phosphorylation level of glycogen synthase kinase-3β (GSK-3β), leading to the inhibition of liver regeneration. Further studies showed that AURKA co-localized and interacted with GSK-3β in the cytoplasm of hepatocytes. When phosphorylation of GSK-3β was enhanced, the total GSK-3β level remained unchanged, while AURKA was not affected, and β-catenin protein levels were increased. In addition, AURKA inhibition affected the formation and proliferation of human liver organoids.Furthermore, AURKA inhibition led to the polarization of M1 macrophages and the release of interleukin-6 and Tumour necrosis factor α, which also led to reduced liver regeneration and increased liver injury. Conclusions:These results provide more details on the mechanism of liver regeneration and suggest that AURKA is an important regulator of this mechanism.

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Regeneration and activation of liver progenitor cells in liver cirrhosis

Cited by 5 publications

References 35 publications

The bright side of fibroblasts: molecular signature and regenerative cues in major organs

The bright side of fibroblasts: molecular signature and regenerative cues in major organs

Spontaneously Ruptured Hepatocellular Carcinoma: Computed Tomography-Based Assessment

Aurora kinase A regulates liver regeneration through macrophages polarization and Wnt/β‐catenin signalling

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