Apelin promotes hepatic fibrosis through ERK signaling in LX-2 cells

Wang, Ying; Song, Jiayi; Bian, Hongyan; Bo, Jiaqi; Lv, Shuangyu; Pan, Weitong; Lv, Xinrui

doi:10.1007/s11010-019-03581-0

Cited by 34 publications

(23 citation statements)

References 39 publications

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“…The expression of phos-ERK is positively correlated with the expression of alpha-SMA in HCC patients [36]. In hepatic cell line, apelin could activate ERK signaling to increase alpha-SMA, collagen I and cyclin D1 [37]. ERK signaling could activate type I collagen in fibroblasts [38].…”

Section: Discussionmentioning

confidence: 99%

Liver Fibrosis and Inflammation under the Control of ERK2

Jeng

Wang

et al. 2020

IJMS

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Chronic liver injury could lead the formation of liver fibrosis, eventually some would develop to hepatocellular carcinoma (HCC), one of the leading malignancies worldwide. The aim of the study is to dissect the role of extracellular signal-regulated kinase 2 (ERK2) signaling in liver fibrosis and inflammation. The choline-deficient, ethionine-supplemented (CDE) diet could lead to fatty livers and generate oval cells, activate hepatocyte stellate cell (HSC) and recruit immune cells as the liver fibrosis model mice. WT and ERK2 deficient (ERK2−/−) mice were compared in terms of liver weight/body weight, liver function, liver fibrosis markers and the differential gene expression in hepatotoxicity. ERK2−/− mice display the less degree of liver fibrosis when compared to WT mice. The protein level of alpha smooth muscle (α-SMA) was reduced and several hepatocellular carcinoma-related genes such as MMP9, FoxM1 were down-regulated. In addition, the cell proliferation and the percentages of activated T cells were reduced in ERK2−/− mice upon liver injury. Therefore, ERK2 plays an important role in regulating liver cirrhosis and inflammation.

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Section: Discussionmentioning

confidence: 99%

Liver Fibrosis and Inflammation under the Control of ERK2

Jeng

Wang

et al. 2020

IJMS

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“…For example, apelin is upregulated in the intestinal epithelial cells of IBD patients and highly expressed in the mesenteric adipose tissue of Crohn’s disease patients[ 27 , 28 ]. Another study group showed that apelin is promoting hepatic fibrosis[ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Prevalence and risk factors of nonalcoholic fatty liver disease in patients with inflammatory bowel diseases: A cross-sectional and longitudinal analysis

Hoffmann

Jung

Behnisch

et al. 2020

WJG

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BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is common in the German population, with an even higher prevalence in inflammatory bowel disease patients. AIM To investigate the risk factors for NAFLD in inflammatory bowel disease patients. METHODS This monocentric retrospective study with a cross-sectional and a longitudinal part included 694 patients. Inclusion criteria were diagnosed inflammatory bowel disease, age ≥ 18 years, availability of at least one abdominal ultrasound. Patients with infectious or suspected alcoholic fatty liver disease were excluded. NAFLD was defined by increased echogenicity at liver ultrasound. Demographic characteristics, disease activity and medications were analyzed as potential risk factors. Parameters influencing the course of NAFLD were identified by a generalized linear mixed model. RESULTS Forty-eight percent of Crohn’s disease (CD) patients and 44% of ulcerative colitis patients suffered from NAFLD. Its occurrence was associated with greater age, hypertension and body mass index (BMI) in both groups, and with higher disease activity and dyslipidemia in CD. 2467 ultrasound results were included in the longitudinal analysis. Risk factors for NAFLD were age, BMI, higher disease activity, bowel resection(s), endoscopic activity and azathioprine use in CD; and BMI and endoscopic activity in ulcerative colitis. CONCLUSION NAFLD was highly prevalent in this cohort of German inflammatory bowel disease patients. Its risk increased mainly with rising age and BMI. This analysis provides a rationale for non-invasive liver screening in inflammatory bowel disease patients.

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“…In vitro, apelin has also demonstrated a significant potential to promote liver fibrosis. It acts directly on LX-2 cells (a cell line used as a reliable in vitro model of HSC) through Erk signalling [179], stimulating cell survival and the synthesis of PDGF-β receptor and collagen-I in these cells [118]. In turn, PDGF-β and LPS can stimulate the expression of APJ, expanding and perpetuating HSC activation [180].…”

Section: Involvement Of the Apelin System In The Pathogenesis Of Lmentioning

confidence: 99%

Roles of the Hepatic Endocannabinoid and Apelin Systems in the Pathogenesis of Liver Fibrosis

Melgar-Lesmes

Perramón

Jiménez

2019

Cells

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Hepatic fibrosis is the consequence of an unresolved wound healing process in response to chronic liver injury and involves multiple cell types and molecular mechanisms. The hepatic endocannabinoid and apelin systems are two signalling pathways with a substantial role in the liver fibrosis pathophysiology—both are upregulated in patients with advanced liver disease. Endogenous cannabinoids are lipid-signalling molecules derived from arachidonic acid involved in the pathogenesis of cardiovascular dysfunction, portal hypertension, liver fibrosis, and other processes associated with hepatic disease through their interactions with the CB1 and CB2 receptors. Apelin is a peptide that participates in cardiovascular and renal functions, inflammation, angiogenesis, and hepatic fibrosis through its interaction with the APJ receptor. The endocannabinoid and apelin systems are two of the multiple cell-signalling pathways involved in the transformation of quiescent hepatic stellate cells into myofibroblast like cells, the main matrix-producing cells in liver fibrosis. The mechanisms underlying the control of hepatic stellate cell activity are coincident despite the marked dissimilarities between the endocannabinoid and apelin signalling pathways. This review discusses the current understanding of the molecular and cellular mechanisms by which the hepatic endocannabinoid and apelin systems play a significant role in the pathophysiology of liver fibrosis.

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Apelin promotes hepatic fibrosis through ERK signaling in LX-2 cells

Cited by 34 publications

References 39 publications

Liver Fibrosis and Inflammation under the Control of ERK2

Liver Fibrosis and Inflammation under the Control of ERK2

Prevalence and risk factors of nonalcoholic fatty liver disease in patients with inflammatory bowel diseases: A cross-sectional and longitudinal analysis

Roles of the Hepatic Endocannabinoid and Apelin Systems in the Pathogenesis of Liver Fibrosis

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