Expression of hepatic progenitor cell markers in acute cellular rejection of liver allografts—An immunohistochemical study

Lo, Ronald; Chan, Kristy Kwan‐Shuen; Leung, Constant; Ng, Irene Oi–Lin

doi:10.1111/ctr.13203

Cited by 2 publications

(3 citation statements)

References 18 publications

(32 reference statements)

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“…For this experiment, 1 × 10 7 of apoHPC-MPs, apoHep-MPs and apoLTC-MPs were intrasplenically injected into DEN-treated rats and liver slices were acquired for fluorescence detection 30 min after injection. The expression of the HPC marker CK19 in liver sections was examined [ 24 – 26 ]. As observed in cell culture, accumulation of red fluorescent apoHPC-MPs, rather than apoHep-MPs and apoLTC-MPs, was found in CK19-positive HPCs (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Extracellular microparticles derived from hepatic progenitor cells deliver a death signal to hepatoma-initiating cells

et al. 2022

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The malignant transformation of normal resident hepatic stem/progenitor cells has a critical role in hepatocarcinogenesis and the recurrence of hepatocellular carcinoma (HCC). We defined such hepatic progenitor cells as hepatoma-initiating cells. An efficient strategy is required to target and kill the hepatoma-initiating cells. We isolated extracellular microparticles (MPs) derived from apoptotic hepatic progenitor cells (HPCs) and tested their ability to inhibit hepatocarcinogenesis. Extracellular MPs were isolated from HPCs, hepatocytes and liver tumor cells. Their effects on tumor growth were investigated in rat primary HCC models, in which hepatocarcinogenesis is induced by diethylnitrosamine (DEN). The extracellular MPs derived from apoptotic HPCs, apoptotic hepatocytes and apoptotic liver tumor cells were similar in morphology, diameter and zeta potential. However, they had different antitumor effects. In DEN-exposed rats, only the MPs derived from apoptotic HPCs effectively inhibit hepatocarcinogenesis. In vitro and in vivo analyses confirmed that HPCs preferentially take up MPs derived from apoptotic HPCs compared to MPs from other liver cell types. Proteomic analysis of MPs from apoptotic HPCs showed enrichment of proteins involved in cell death pathways. Thus, HPC-derived MPs contain a death signal to induce the killing of hepatoma-initiating cells. Our findings provide evidence that a death signal encapsulated in HPC-derived extracellular microparticles can efficiently clear hepatoma-initiating cells and prevent hepatocarcinogenesis. Graphical Abstract

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Section: Resultsmentioning

confidence: 99%

“…After 24 h, liver slices were acquired for fluorescence detection. HPCs were labeled with an antibody against SOX9 [ 26 , 27 ] and apoptotic cells were detected with an antibody against cleaved caspase 3. The highest number of apoptotic HPCs (positive for both SOX9 and cleaved caspase 3) was seen in the apoHPC-MPs treatment group (Fig.…”

Section: Resultsmentioning

confidence: 99%

Extracellular microparticles derived from hepatic progenitor cells deliver a death signal to hepatoma-initiating cells

et al. 2022

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“…In this study, we treated C57BL/6 mice with five broad‐spectrum antibiotics for 14 days at the maximum dose to eliminate their gut microbes. Subsequently, we assessed the serum biochemical indices and quantified the expression of the progenitor cell marker SRY‐related high mobility group‐box gene 9 (SOX9) (Lo, Chan, Leung, & Ng, ; Pozniak et al, ; Tarlow, Finegold, & Grompe, ). The plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were not significantly higher in the treated mice than they were in the control mice, but the triglyceride (TG), lactate dehydrogenase (LDH), low‐density lipoprotein (LDL), and high‐density lipoprotein (HDL) concentrations were all affected.…”

Section: Introductionmentioning

confidence: 99%

Hepatic progenitor cell activation is induced by the depletion of the gut microbiome in mice

Wang

Sun

et al. 2019

MicrobiologyOpen

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The homeostasis of the gut microbiome is crucial for human health and for liver function. However, it has not been established whether the gut microbiome influence hepatic progenitor cells (HPCs). HPCs are capable of self‐renewal and differentiate into hepatocytes and cholangiocytes; however, HPCs are normally quiescent and are rare in adults. After sustained liver damage, a ductular reaction occurs, and the number of HPCs is substantially increased. Here, we administered five broad‐spectrum antibiotics for 14 days to deplete the gut microbiomes of male C57BL/6 mice, and we measured the plasma aminotransferases and other biochemical indices. The expression levels of two HPC markers, SRY‐related high mobility group‐box gene 9 (Sox9) and cytokeratin (CK), were also measured. The plasma aminotransferase activities were not affected, but the triglyceride, lactate dehydrogenase, low‐density lipoprotein, and high‐density lipoprotein concentrations were significantly altered; this suggests that liver function is affected by the composition of the gut microbiome. The mRNA expression of Sox9 was significantly higher in the treated mice than it was in the control mice (p < 0.0001), and a substantial expression of Sox9 and CK was observed around the bile ducts. The mRNA expression levels of proinflammatory factors (interleukin [IL]‐1β, IL‐6, tumor necrosis factor [TNF]‐α, and TNF‐like weak inducer of apoptosis [Tweak]) were also significantly higher in the antibiotic‐treated mice than the levels in the control mice. These data imply that the depletion of the gut microbiome leads to liver damage, negatively impacts the hepatic metabolism and function, and activates HPCs. However, the underlying mechanisms remain to be determined.

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Expression of hepatic progenitor cell markers in acute cellular rejection of liver allografts—An immunohistochemical study

Abstract: Expression HPC markers were correlated with clinical and histological parameters in ACR. Expression of each individual marker may be more tightly associated with a particular component of the ACR process.

Cited by 2 publications

References 18 publications

Extracellular microparticles derived from hepatic progenitor cells deliver a death signal to hepatoma-initiating cells

Extracellular microparticles derived from hepatic progenitor cells deliver a death signal to hepatoma-initiating cells

Hepatic progenitor cell activation is induced by the depletion of the gut microbiome in mice

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