Overexpression of c-myc in hepatocytes promotes activation of hepatic stellate cells and facilitates the onset of liver fibrosis

Nevzorova, Yulia A.; Hu, Wei Shou; Cubero, Francisco Javier; Haas, Ute; Freimuth, Julia; Tacke, Frank; Liedtke, Christian

doi:10.1016/j.bbadis.2013.06.001

Cited by 78 publications

(51 citation statements)

References 35 publications

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“…Recently, several studies suggested there existed crosstalk between hepatocytes and HSC, such as overexpression of c-Myc, p53 in hepatocytes contributed to HSC activation3637, yet hepatic HNF1a showed antifibrotic function. However, the role of hepatocytes in the activation of HSCs during chronic HBV infection progressed into liver cirrhosis has not been clearly elucidated.…”

Section: Discussionmentioning

confidence: 99%

Hepatic SATB1 induces paracrine activation of hepatic stellate cells and is upregulated by HBx

Gong

Han

et al. 2016

Sci Rep

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Chronic hepatitis B virus (HBV) infection is a major cause of chronic liver diseases, but its involvement in hepatic fibrogenesis remains unclear. Special AT-rich binding protein 1 (SATB1) has been implicated in reprogramming chromatin organization and transcription profiles in many cancers and non-cancer-related conditions. We found that hepatic SATB1 expression was significantly up-regulated in fibrotic tissues from chronic hepatitis B virus (HBV)-infected patients and HBV transgenic (HBV-Tg) mouse model. Knockdown of SATB1 in the liver significantly alleviated CCl4-induced fibrosis in HBV-Tg mouse model. Moreover, we suggested HBV encoded x protein (HBx) induced SATB1 expression through activation of JNK and ERK pathways. Enforced expression of SATB1 in hepatocytes promoted the activation and proliferation of hepatic stellate cells (HSCs) by secretion of connective tissue growth factor (CTGF), Interleukin-6 (IL-6) and platelet derived growth factor-A (PDGF-AA). Our findings demonstrated that HBx upregulated hepatic SATB1 which exerted pro-fibrotic effects by paracrine activation of stellate cells in HBV-related fibrosis.

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Section: Discussionmentioning

confidence: 99%

Hepatic SATB1 induces paracrine activation of hepatic stellate cells and is upregulated by HBx

Gong

Han

et al. 2016

Sci Rep

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“…This effect is mediated in part by an inhibition of PPARγ and reduction of lipogenesis, plus increased PDGF-B expression in hepatocytes and subsequent paracrine crosstalk with HSCs. Interestingly, the increase in c-myc may result either from a direct inflammatory response to liver injury or from injury-induced gene amplification [139]. C-myc may be a target for HCC chemoprevention and fibrosis modulation.…”

Section: New and Emerging Pathways Of Hsc Activationmentioning

confidence: 98%

“…For example, c-myc is a central driver of cellular proliferation [137] and its amplification is commonly found in HCC [138]. It has recently been shown to be overexpressed in hepatocytes of human liver samples with advanced fibrosis and promotes a "profibrotic tissue environment" via pre-activation of HSCs, which primes them for a second profibrotic insult [139]. This effect is mediated in part by an inhibition of PPARγ and reduction of lipogenesis, plus increased PDGF-B expression in hepatocytes and subsequent paracrine crosstalk with HSCs.…”

Section: New and Emerging Pathways Of Hsc Activationmentioning

confidence: 99%

Stellate Cells and Hepatic Fibrosis

Hasegawa

Wallace

Friedman

2015

Stellate Cells in Health and Disease

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“…The Myc proteins are involved in major biological processes including proliferation, metabolism, cell cycle progression, apoptosis, cell growth and differentiation, fibrosis, and polarity (34)(35)(36) (Figure 1). All of these cellular functions are altered and ongoing in ADPKD.…”

Section: Myc Cellular Functionsmentioning

confidence: 99%

c-Myc Signalling in the Genetic Mechanism of Polycystic Kidney Disease

Trudel

2015

Polycystic Kidney Disease

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Licence: This open access article is licenced under Creative Commons Attribution 4.0 International (CC BY 4.0). http://creativecommons.org/licenses/by/4.0/ Users are allowed to share (copy and redistribute the material in any medium or format) and adapt (remix, transform, and build upon the material for any purpose, even commercially), as long as the author and the publisher are explicitly identified and properly acknowledged as the original source. AbstractThe Myc family of transcription factors regulates major biological processes such as proliferation, stem/progenitor cell pluripotency, metabolism, apoptosis, cell growth and differentiation. The most-studied member c-Myc is essential in embryonic development and cellular homeostasis. Dysregulation of c-Myc protein function is not only associated with malignant transformation and human tumors but is also implicated in autosomal dominant polycystic kidney disease (ADPKD), a human genetic disorder, considered a neoplasia in disguise. Studies from human ADPKD kidneys, caused by mutation in the

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Overexpression of c-myc in hepatocytes promotes activation of hepatic stellate cells and facilitates the onset of liver fibrosis

Abstract: Overexpression of c-myc is a novel marker of liver fibrosis in man and mice. We conclude that chronic induction of c-myc especially in hepatocytes has the potential to prime resident HSC for activation, proliferation and myofibroblast differentiation.

Cited by 78 publications

References 35 publications

Hepatic SATB1 induces paracrine activation of hepatic stellate cells and is upregulated by HBx

Hepatic SATB1 induces paracrine activation of hepatic stellate cells and is upregulated by HBx

Stellate Cells and Hepatic Fibrosis

c-Myc Signalling in the Genetic Mechanism of Polycystic Kidney Disease

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