The hepatic effects of GDF11 on health and disease

Gerardo-Ramírez, Monserrat; German-Ramirez, N.; Escobedo-Calvario, Alejandro; Chávez-Rodríguez, Lisette; Bucio, Leticia; Souza-Arroyo, Verónica; Miranda-Labra, Roxana U.; Gutiérrez‐Ruiz, María Concepción; Gómez–Quiroz, Luis E.

doi:10.1016/j.biochi.2022.12.017

Cited by 4 publications

(4 citation statements)

References 56 publications

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“…The effect of GDF11 on the liver is still controversial. [ 9 ] The study of sh‐GDF11 on ALF has not been reported. GalN, a kind of hepatotoxin inhibiting protein and RNA synthesis, can lead to fatal liver failure in combination with LPS.…”

Section: Discussionmentioning

confidence: 99%

“…[ 7 ] Intriguingly, adeno‐associated viruses‐GDF11 and recombinant GDF11 protein may severely impair liver regeneration, whereas suppression of GDF11 activity with neutralizing antibodies leads to opposite trend after partial hepatectomy. [ 8,9 ] However, the role of GDF11 in ALF has remained unknown. Gene therapy is a research hotspot currently, and specifically, recombinant adenoviruses have been extensively studied and applied in clinical trials for cancer and vaccines.…”

Section: Introductionmentioning

confidence: 99%

“…[7] Intriguingly, adeno-associated viruses-GDF11 and recombinant GDF11 protein may severely impair liver regeneration, whereas suppression of GDF11 activity with neutralizing antibodies leads to opposite trend after partial hepatectomy. [8,9] However, the role of GDF11 in ALF has remained unknown.…”

mentioning

confidence: 99%

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Silencing of GDF11 suppresses hepatocyte apoptosis to relieve LPS/D‐GalN acute liver failure

Zhou,

Li,

Wang

et al. 2023

J Biochem & Molecular Tox

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In this paper, we generated a short hairpin RNA growth differentiation factor‐11 (sh‐GDF11) and evaluated the effects of sh‐GDF11 on the pathogenesis of acute liver failure (ALF) in vitro and in vivo. Through bioinformatics study, the key gene related to ALF was assayed. Lipopolysaccharide (LPS) and D‐galactoamine (D‐GalN) were applied to establish the mouse model of LPS/D‐GalN‐induced liver injury, and TNF‐α and D‐Gal were used to construct an in vitro cell model, followed by treatment of sh‐GDF11 for analysis of liver cell proliferation. Bioinformatics analysis showed that the protective effect of sh‐GDF11 on ALF may be mediated by phosphatidylinositol‐3‐kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. The results of in vitro study found that sh‐GDF11 could promote cell proliferation and inhibit death by blocking the PI3K/Akt/mTOR signaling pathway. In vivo animal experiments further confirmed that sh‐GDF11 could suppress hepatocyte apoptosis by inhibiting the PI3K/Akt/mTOR signaling pathway. sh‐GDF11 relieved LPS/D‐GalN‐induced ALF by blocking the PI3K/Akt/mTOR signaling pathway, emphasizing its critical role in LPS/D‐GalN‐induced ALF treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Silencing of GDF11 suppresses hepatocyte apoptosis to relieve LPS/D‐GalN acute liver failure

Zhou,

Li,

Wang

et al. 2023

J Biochem & Molecular Tox

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“…9 GDF11 regulates gene expression in different tissues via activating SMAD and non-SMAD pathways. 9 GDF11 affects various biological functions including reducing inflammation, 24 lipid homeostasis, 25 angiogenesis 26 and anti-fibrotic properties. 14 Moreover, GDF11 participates in the pathogenesis of various disorders such as diabetes mellitus, 27 cardiovascular diseases, 28 metabolic disorders, 29 cancer 18 and aging.…”

Section: The Physiological Roles Of Gdf11 In the Bodymentioning

confidence: 99%

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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