Signaling pathways of liver regeneration: Biological mechanisms and implications

Zhang, Chunyan; Sun, Caifang; Zhao, Yabin; Ye, Bingyu; Yu, GuoYing

doi:10.1016/j.isci.2023.108683

Cited by 7 publications

(2 citation statements)

References 225 publications

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“…While TGF-β aids in liver differentiation and regeneration, its excessive presence due to chronic damage triggers stellate cell activation, hepatocyte death, and ultimately, fibrosis and cirrhosis. Initially, during liver tumor formation, TGF-β may suppress growth, but prolonged signaling activation can later promote tumor progression [38,39].…”

Section: Discussionmentioning

confidence: 99%

Serum Levels of miR-122-5p and miR-125a-5p Predict Hepatotoxicity Occurrence in Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation

Mikulski,

Kościelny,

Dróżdż

et al. 2024

IJMS

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Hepatic complications are an acknowledged cause of mortality and morbidity among patients undergoing hematopoietic stem cell transplantation. In this study, we aimed to evaluate the potential role in the prediction of liver injury of five selected microRNAs (miRNAs)—miR-122-5p, miR-122-3p, miR-15b-5p, miR-99b-5p, and miR-125a-5p—in the setting of autologous hematopoietic stem cell transplantation (ASCT). A total of 66 patients were included in the study: 50 patients (75.8%) with multiple myeloma (MM) and 16 (24.2%) with lymphoma. Blood samples were collected after the administration of the conditioning regimen, on the day of transplant (day 0). The expression levels of selected miRNAs were quantified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) using the miRCURY LNA miRNA Custom PCR Panels (QIAGEN). In a multivariate logistic regression analysis adjusted for age, sex, and the administered conditioning regimen, two miRNAs, hsa-miR-122-5p (odds ratio, OR 2.10, 95% confidence interval, CI: 1.29–3.42, p = 0.0029) and hsa-miR-125a-5p (OR 0.27, 95% CI: 0.11–0.71, p = 0.0079), were independent for hepatic toxicity occurrence during the 14 days after transplant. Our model in 10-fold cross-validation preserved its diagnostic potential with a receiver operating characteristics area under the curve (ROC AUC) of 0.75, 95% CI: 0.63–0.88 and at optimal cut-off reached 72.0% sensitivity and 74.4% specificity. An elevated serum level of miR-122-5p and decreased level of miR-125a-5p on day 0 are independent risk factors for hepatotoxicity in ASCT recipients, showing promise in accurately predicting post-ASCT complications. Identifying patients susceptible to complications has the potential to reduce procedure costs and optimize the selection of inpatient or outpatient procedures.

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Section: Discussionmentioning

confidence: 99%

Serum Levels of miR-122-5p and miR-125a-5p Predict Hepatotoxicity Occurrence in Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation

Mikulski,

Kościelny,

Dróżdż

et al. 2024

IJMS

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“…Maintaining a balance between various sphingolipid metabolites such as ceramide, sphingosine, and S1P is crucial for cellular homeostasis and various physiological processes [ 2 ]. Numerous studies have shown that the activation of signaling pathways such as HGF, EGFR, TGF-β, TNF-α, and inflammatory pathways (NF-κB, STAT3) promotes liver regeneration, and the activation of IL-6 and IL-8 signaling pathways may lead to tumor-associated inflammation and development of HCC [ 3 , 4 , 5 , 6 ]. In contrast to these signals, sphingolipids are not only essential components of cell membranes, but also function as autocrine and paracrine mediators that contribute to regeneration and HCC development [ 7 , 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Critical Roles of the Sphingolipid Metabolic Pathway in Liver Regeneration, Hepatocellular Carcinoma Progression and Therapy

Nojima,

Shimizu,

Murakami

et al. 2024

Cancers

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The sphingolipid metabolic pathway, an important signaling pathway, plays a crucial role in various physiological processes including cell proliferation, survival, apoptosis, and immune regulation. The liver has the unique ability to regenerate using bioactive lipid mediators involving multiple sphingolipids, including ceramide and sphingosine 1-phosphate (S1P). Dysregulation of the balance between sphingomyelin, ceramide, and S1P has been implicated in the regulation of liver regeneration and diseases, including liver fibrosis and hepatocellular carcinoma (HCC). Understanding and modulating this balance may have therapeutic implications for tumor proliferation, progression, and metastasis in HCC. For cancer therapy, several inhibitors and activators of sphingolipid signaling, including ABC294640, SKI-II, and FTY720, have been discussed. Here, we elucidate the critical roles of the sphingolipid pathway in the regulation of liver regeneration, fibrosis, and HCC. Regulation of sphingolipids and their corresponding enzymes may considerably influence new insights into therapies for various liver disorders and diseases.

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Blood flow‐induced angiocrine signals promote organ growth and regeneration

Follert,

Große‐Segerath,

Lammert

2024

BioEssays

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Recently, we identified myeloid‐derived growth factor (MYDGF) as a blood flow‐induced angiocrine signal that promotes human and mouse hepatocyte proliferation and survival. Here, we review literature reporting changes in blood flow after partial organ resection in the liver, lung, and kidney, and we describe the angiocrine signals released by endothelial cells (ECs) upon blood flow alterations in these organs. While hepatocyte growth factor (HGF) and MYDGF are important angiocrine signals for liver regeneration, by now, angiocrine signals have also been reported to stimulate hyperplasia and/or hypertrophy during the regeneration of lungs and kidneys. In addition, angiocrine signals play a critical role in tumor growth. Understanding the mechano‐elastic properties and flow‐mediated alterations in the organ‐specific microvasculature is crucial for therapeutic approaches to maintain organ health and initiate organ renewal.

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Signaling pathways of liver regeneration: Biological mechanisms and implications

Cited by 7 publications

References 225 publications

Serum Levels of miR-122-5p and miR-125a-5p Predict Hepatotoxicity Occurrence in Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation

Serum Levels of miR-122-5p and miR-125a-5p Predict Hepatotoxicity Occurrence in Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation

Critical Roles of the Sphingolipid Metabolic Pathway in Liver Regeneration, Hepatocellular Carcinoma Progression and Therapy

Blood flow‐induced angiocrine signals promote organ growth and regeneration

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