CDH11 promotes liver fibrosis via activation of hepatic stellate cells

Ruan, Wanyuan; Pan, Runsang; Shen, Xiaoxu; Nie, Yingjie; Yayun, Wu

doi:10.1016/j.bbrc.2018.11.153

Cited by 19 publications

(25 citation statements)

References 17 publications

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“…In addition to the well-known activated HSCs markers, some of the most significant DEGs that were identified by RNA sequencing played a critical role in HSC activation or liver fibrosis. Among these genes, CDH11 [22,23], CTHRC1 [24], FMOD [25], and PRRX1 [26] facilitated HSC activation; Larp6 promoted type I collagen production and was a potential anti-fibrotic target [27,28]; HHIP, a Hedgehog pathway antagonist, inhibited HSC activation and was downregulated in activated HSCs [29]. Moreover, we also evaluated the changes in the expression of the most significant DEGs in TGF-β1-treated LX-2 cells, which is an in vitro human HSC activation model ( Fig 4F).…”

Section: Rna Sequencing Of Quiescent and Activated Primary Hscsmentioning

confidence: 99%

Expression of hepatic stellate cell activation-related genes in HBV-, HCV-, and nonalcoholic fatty liver disease-associated fibrosis

et al. 2020

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Liver fibrosis is a manifestation of chronic liver injury. It leads to hepatic dysfunction and is a critical element in the pathogenesis of cirrhosis and hepatocellular carcinoma. The activation of hepatic stellate cells (HSC) plays a central role in liver fibrogenesis of different etiologies. To elucidate the molecular mechanism of this phenomenon, it is important to analyze the changes in gene expression that accompany the HSC activation process. In this study, we isolated quiescent and activated HSCs from control mice and mice with CCl 4-induced liver fibrosis, respectively, and performed RNA sequencing to compare the differences in gene expression patterns between the two types of HSCs. We also reanalyzed public gene expression data for fibrotic liver tissues isolated from patients with HBV infection, HCV infection, and nonalcoholic fatty liver disease to investigate the gene expression changes during liver fibrosis of these three etiologies. We detected 146 upregulated and 18 downregulated genes in activated HSCs, which were implicated in liver fibrosis as well. Among the overlapping genes, seven transcription factor-encoding genes, ARID5B, GATA6, MITF, PBX1, PLAGL1, SOX4, and SOX9, were upregulated, while one, RXRA, was downregulated. These genes were suggested to play a critical role in HSC activation, and subsequently, in the promotion of liver fibrosis. We undertook the RNA sequencing of quiescent and activated HSCs and analyzed the expression profiles of genes associated with HSC activation in liver fibrotic tissues from different liver diseases, and also aimed to elucidate the changes in gene expression patterns associated with HSC activation and liver fibrosis.

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Section: Rna Sequencing Of Quiescent and Activated Primary Hscsmentioning

confidence: 99%

Expression of hepatic stellate cell activation-related genes in HBV-, HCV-, and nonalcoholic fatty liver disease-associated fibrosis

et al. 2020

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“…In the murine liver, expression of cadherin-11 is low in the healthy organ but increased upon CCl 4 treatment on hepatocytes, HSCs and macrophages (Table 2) [135]. Also, in human livers cadherin-11 levels correlated with the fibrosis stage [136]. Genetic deletion of cadherin-11 protected mice from CCl 4 -induced liver fibrosis and resulted in reduced expression of collagen I and αSMA as judged by immunohistochemical analysis and quantitative PCR [135].…”

Section: Cadherinsmentioning

confidence: 99%

The Many Roles of Cell Adhesion Molecules in Hepatic Fibrosis

Hintermann

Christen

2019

Cells

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Fibrogenesis is a progressive scarring event resulting from disrupted regular wound healing due to repeated tissue injury and can end in organ failure, like in liver cirrhosis. The protagonists in this process, either liver-resident cells or patrolling leukocytes attracted to the site of tissue damage, interact with each other by soluble factors but also by direct cell–cell contact mediated by cell adhesion molecules. Since cell adhesion molecules also support binding to the extracellular matrix, they represent excellent biosensors, which allow cells to modulate their behavior based on changes in the surrounding microenvironment. In this review, we focus on selectins, cadherins, integrins and members of the immunoglobulin superfamily of adhesion molecules as well as some non-classical cell adhesion molecules in the context of hepatic fibrosis. We describe their liver-specific contributions to leukocyte recruitment, cell differentiation and survival, matrix remodeling or angiogenesis and touch on their suitability as targets in antifibrotic therapies.

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“…After liver injury, the wound-healing response will lead to the accumulation of extracellular matrix (ECM) [6], and the continuous ECM accumulation in liver injury would damage normal liver function and leads to LF-cirrhosis-liver cancer [7]. Meanwhile, activated hepatic stellate cells (HSCs) mainly produce a large amount of collagen and ECM during the process of fibrosis [8]. Therefore, considering that there are no effective therapies for LF, effective treatment approaches for inactivation and anti-proliferation of HSCs to LF, as well as the underlying regulatory mechanisms of LF, are desperately needed.…”

Section: Introductionmentioning

confidence: 99%

PRC1 promotes GLI1-dependent osteopontin expression in association with the Wnt/β-catenin signaling pathway and aggravates liver fibrosis

Xiang

Huang

et al. 2019

Cell Biosci

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BackgroundPRC1 (Protein regulator of cytokinesis 1) regulates microtubules organization and functions as a novel regulator in Wnt/β-catenin signaling pathway. Wnt/β-catenin is involved in development of liver fibrosis (LF). We aim to investigate effect and mechanism of PRC1 on liver fibrosis.MethodsCarbon tetrachloride (CCl4)-induced mice LF model was established and in vitro cell model for LF was induced by mice primary hepatic stellate cell (HSC) under glucose treatment. The expression of PRC1 in mice and cell LF models was examined by qRT-PCR (quantitative real-time polymerase chain reaction), western blot and immunohistochemistry. MTT assay was used to detect cell viability, and western blot to determine the underlying mechanism. The effect of PRC1 on liver pathology was examined via measurement of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and hydroxyproline, as well as histopathological analysis.ResultsPRC1 was up-regulated in CCl4-induced mice LF model and activated HSC. Knockdown of PRC1 inhibited cell viability and promoted cell apoptosis of activated HSC. PRC1 expression was regulated by Wnt3a signaling, and PRC1 could regulate downstream β-catenin activation. Moreover, PRC1 could activate glioma-associated oncogene homolog 1 (GLI1)-dependent osteopontin expression to participate in LF. Adenovirus-mediated knockdown of PRC1 in liver attenuated LF and reduced collagen deposition.ConclusionsPRC1 aggravated LF through regulating Wnt/β-catenin mediated GLI1-dependent osteopontin expression, providing a new potential therapeutic target for LF treatment.

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CDH11 promotes liver fibrosis via activation of hepatic stellate cells

Cited by 19 publications

References 17 publications

Expression of hepatic stellate cell activation-related genes in HBV-, HCV-, and nonalcoholic fatty liver disease-associated fibrosis

Expression of hepatic stellate cell activation-related genes in HBV-, HCV-, and nonalcoholic fatty liver disease-associated fibrosis

The Many Roles of Cell Adhesion Molecules in Hepatic Fibrosis

PRC1 promotes GLI1-dependent osteopontin expression in association with the Wnt/β-catenin signaling pathway and aggravates liver fibrosis

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