Harnessing liver progenitors in the treatment of liver fibrosis: a step in the right direction?

Breitkopf‐Heinlein, Katja; Syn, Wing Kin

doi:10.1136/gutjnl-2019-320203

Cited by 6 publications

(10 citation statements)

References 12 publications

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“…Liver fibrosis is a complex physiological and pathophysiological condition associated with the mechanisms of cicatrization [ 1 ]. The deposition of extracellular matrix is a central event in liver fibrosis, and the myofibroblasts matrix is mainly produced by activated HSCs [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

N6-methyladenosine modification regulates ferroptosis through autophagy signaling pathway in hepatic stellate cells

et al. 2021

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Ferroptosis is a recently identified non-apoptotic form of cell death characterized by iron-dependent lipid peroxidation. However, the underlying exact mechanisms remain poorly understood. Here, we report that the total levels of N 6 -methyladenosine (m 6 A) modification are evidently increased upon exposure to ferroptosis-inducing compounds due to the upregulation of methylase METTL4 and the downregulation of demethylase FTO. Interestingly, RNA-seq shows that m 6 A modification appears to trigger autophagy activation by stabilizing BECN1 mRNA, which may be the potential mechanism for m 6 A modification-enhanced HSC ferroptosis. Importantly, YTHDF1 is identified as a key m 6 A reader protein for BECN1 mRNA stability, and knockdown of YTHDF1 could prevent BECN1 plasmid-induced HSC ferroptosis. Noteworthy, YTHDF1 promotes BECN1 mRNA stability and autophagy activation via recognizing the m 6 A binding site within BECN1 coding regions. In mice, erastin treatment alleviates liver fibrosis by inducing HSC ferroptosis. HSC-specific inhibition of m 6 A modification could impair erastin-induced HSC ferroptosis in murine liver fibrosis. Moreover, we retrospectively analyzed the effect of sorafenib on HSC ferroptosis and m 6 A modification in advanced fibrotic patients with hepatocellular carcinoma (HCC) receiving sorafenib monotherapy. Attractively, the m 6 A modification upregulation, autophagy activation, and ferroptosis induction occur in human HSCs. Overall, these findings reveal novel signaling pathways and molecular mechanisms of ferroptosis, and also identify m 6 A modification-dependent ferroptosis as a potential target for the treatment of liver fibrosis.

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Section: Introductionmentioning

confidence: 99%

N6-methyladenosine modification regulates ferroptosis through autophagy signaling pathway in hepatic stellate cells

et al. 2021

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“…These LGR5+ LPCs can attenuate liver fibrosis. 7,76 Administration of GDF11, which is elevated in human and mice fibrotic livers, enhanced the expansion of LGR5+ cells in mouse and human liver organoids. 7 In mouse models of hepatic fibrosis, LGR5+ LPCs treated with GDF11 suppressed fibrogenesis.…”

Section: Gdf11 In Liver Fibrosismentioning

confidence: 97%

GDF11: An emerging therapeutic target for liver diseases and fibrosis

Habibi,

Falamarzi,

Ebrahimi

et al. 2024

J Cellular Molecular Medi

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Growth differentiation factor 11 (GDF11), also known as bone morphogenetic protein 11 (BMP11), has been identified as a key player in various biological processes, including embryonic development, aging, metabolic disorders and cancers. GDF11 has also emerged as a critical component in liver development, injury and fibrosis. However, the effects of GDF11 on liver physiology and pathology have been a subject of debate among researchers due to conflicting reported outcomes. While some studies suggest that GDF11 has anti‐aging properties, others have documented its senescence‐inducing effects. Similarly, while GDF11 has been implicated in exacerbating liver injury, it has also been shown to have the potential to reduce liver fibrosis. In this narrative review, we present a comprehensive report of recent evidence elucidating the diverse roles of GDF11 in liver development, hepatic injury, regeneration and associated diseases such as non‐alcoholic fatty liver disease (NAFLD), non‐alcoholic steatohepatitis (NASH), liver fibrosis and hepatocellular carcinoma. We also explore the therapeutic potential of GDF11 in managing various liver pathologies.

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“…Они также способствуют увеличению пролиферации и редукции апоптоза гепатоцитов, росту экспрессии некоторых противовоспалительных и антифиброзных цитокинов с потенциальными гепатотропными свойствами, включая гепатоцитарный фактор роста (HGF), VEGF, основной фактор роста фибробластов (bFGF), плацентарный фактор роста (PIGF), моноцитарный хемоаттрактантный протеин-1, фактор стволовых клеток (SCF)-1, хемокин SDF-1, CD135 или fms-подобную тирозинкиназу 3 (Flt-3), гранулоцитарно-макрофагальный колониестимулирующий фактор (GM-CSF) и многочисленные ИЛ [68]. В добавок стимулированная МСК экспансия гепатоцитов из увеличенной популяции печеночных клеток-предшественников приводит не только к уменьшению выраженности ФП, но и регенерации печени [69].…”

Section: трансплантация мезенхимальных стволовых клетокunclassified

Current strategies for targeted therapy of liver fibrosis

Garbuzenko

2022

Bûll. sib. med.

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Liver fibrosis (LF) is an unfavorable event in the natural course of chronic liver diseases (CLD), therefore, early implementation and widespread use of antifibrotic therapy methods is a pressing issue in hepatology. The aim of the review was to describe current approaches to targeted therapy of LF.PubMed database, Google Scholar search engine, Cochrane Database of Systematic Reviews, eLIBRARY.RU scientific electronic library, as well as reference lists of articles were used to search for scientific articles. The publications that corresponded to the aim of the study were selected for the period from 1998 to 2021 by the terms “liver fibrosis”, “pathogenesis”, and “treatment”. Inclusion criteria were restricted to targeted therapy of LF.Despite the growing evidence for reversibility of LF, there are currently no effective or clinically approved regimens for its specific therapy. However, taking into account the relevance of the issue, scientific research in this area is necessary. Multiple drugs with a good safety profile have been studied, which, though intended for other purposes, can have a positive effect on LF. In addition, a number of innovative approaches that differ from pharmacotherapy inspire optimism about finding a solution to this problem. It is obvious that studies focused on well-characterized groups of patients with confirmed histologic, elastography, clinical, and radiological parameters are required. This is a challenging task, since the key point will be stratification of risk based on ethnicity, etiology, and clinical status, and very large samples will be required for a reliable assessment. Nevertheless, the solution will increase efficiency of treatment for patients with CLD, improve their prognosis and quality of life, and significantly reduce the need for liver transplantation, a demand for which remains extremely high worldwide.

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Harnessing liver progenitors in the treatment of liver fibrosis: a step in the right direction?

Cited by 6 publications

References 12 publications

N6-methyladenosine modification regulates ferroptosis through autophagy signaling pathway in hepatic stellate cells

N6-methyladenosine modification regulates ferroptosis through autophagy signaling pathway in hepatic stellate cells

GDF11: An emerging therapeutic target for liver diseases and fibrosis

Current strategies for targeted therapy of liver fibrosis

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