Bone morphogenetic protein 8B promotes the progression of non-alcoholic steatohepatitis

@article{Vacca2020BoneMP,
  title={Bone morphogenetic protein 8B promotes the progression of non-alcoholic steatohepatitis},
  author={Michele Vacca and Jack Leslie and Sam Virtue and Brian Yee Hong Lam and Olivier Govaere and Dina G. Tiniakos and Sophie Snow and Susan E. Davies and Kasparas Petkevicius and Zhen Tong and Vivian Peirce and Mette Juul Nielsen and Zsuzsanna Ament and Wei Li and Tomasz Kostrzewski and Diana Julie Leeming and Vlad Ratziu and Michael E. D. Allison and Quentin Mark Anstee and Julian Leether Griffin and Fiona Oakley and Antonio Vidal-Puig},
  journal={Nature Metabolism},
  year={2020},
  volume={2},
  pages={514-531}
}
Non-alcoholic steatohepatitis (NASH) is characterized by lipotoxicity, inflammation and fibrosis, ultimately leading to end-stage liver disease. The molecular mechanisms promoting NASH are poorly understood, and treatment options are limited. Here, we demonstrate that hepatic expression of bone morphogenetic protein 8B (BMP8B), a member of the transforming growth factor beta (TGFβ)–BMP superfamily, increases proportionally to disease stage in people and animal models with NASH. BMP8B signals… 

BMP4 and Gremlin 1 regulate hepatic cell senescence during clinical progression of NAFLD/NASH.

It is concluded that senescence is an important driver of human NAFLD/NASH and that BMP4 and Gremlin 1 are novel therapeutic targets.

The role of bone morphogenetic proteins in liver fibrosis

In this review, the recent findings of the dual roles of BMPs in liver fibrosis are summarized and better understanding of the underlying mechanisms of B MPs in the progression of liver disease is critically important for improving their therapeutic effect.

Modelling human liver fibrosis in the context of non-alcoholic steatohepatitis using a microphysiological system

It is demonstrated how the MPS NASH model can be used to model different aspects of clinical NASH but importantly its ability to model advanced disease with a quantifiable fibrosis phenotype is demonstrated.

Pathophysiological mechanisms underlying MAFLD.

Diabetic fibrosis.

TGF-β Signaling in Liver, Pancreas, and Gastrointestinal Diseases and Cancer

The involvement of the TGF-β pathway mediated by the transcriptional regulators SMADs in disease progression to cancer in the digestive system is reviewed and clues toward understanding and managing the complexity of the pathway in disease and cancer are provided.

Bone Morphogenetic Protein Signaling in Liver and Gastrointestinal Diseases and Cancer

  • Biology, Medicine
  • 2021
Although the TGF-b and BMP families signal through distinct receptor complexes and through distinct SMAD complexes, the pathways intersect at SMAD4, SMAD6, and SMAD7, and these pathways can have cooperative or counteracting effects through the genes that they regulate.

The Emerging Factors and Treatment Options for NAFLD-Related Hepatocellular Carcinoma

The development of diagnostic methods and novel biomarkers, as well as the combined evaluation algorithm and artificial intelligence, support the early and precise diagnosis of NAFLD-related HCC, and timely monitoring during its progression is essential for improving treatment and prognosis.

References

SHOWING 1-10 OF 64 REFERENCES

A Microphysiological System for Studying Nonalcoholic Steatohepatitis

It is demonstrated that in co‐culture the PNPLA3 I148M mutation alone can cause hepatic stellate cells to enhance the overall NASH disease phenotype and produce a more pro‐inflammatory milieu.

Therapeutic inhibition of inflammatory monocyte recruitment reduces steatohepatitis and liver fibrosis

Pharmacological inhibition of CCR2+ monocyte recruitment efficiently ameliorates insulin resistance, hepatic inflammation, and fibrosis, corroborating the therapeutic potential of CVC in patients with NASH.

An improved mouse model that rapidly develops fibrosis in non-alcoholic steatohepatitis

An improved CDAHFD model may be a mouse model of rapidly progressive liver fibrosis and be potentially useful for better understanding human NASH disease and in the development of efficient therapies for this condition.

Triggering and resolution of inflammation in NASH

The authors comprehensively discuss the key factors that trigger hepatic inflammation, as well as the pathways involved in inflammation resolution, which help to design targeted therapies able to halt or reverse disease progression in NASH.

Lipid zonation and phospholipid remodeling in nonalcoholic fatty liver disease

NAFLD is associated not only with lipid enrichment, but also with zonal changes of specific lipids and their associated metabolic pathways, which may play a role in the heterogeneous development of NAFLD.

BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism

Data support a key role for BMP6 as a ligand for hemojuvelin and an endogenous regulator of hepcidin expression and iron metabolism in vivo, and demonstrate a physical interaction between HJV.Fc and Bmp6.

Bone morphogenetic protein 2 inhibits hepatocellular carcinoma growth and migration through downregulation of the PI3K/AKT pathway

BMP-2 exerts an inhibitory effect on the growth and migration of HCC cells, possibly via a blockade of PI3K/AKT signaling.

Serum levels of osteoprotegerin in the spectrum of nonalcoholic fatty liver disease

Serum osteoprotegerin concentrations are reduced in patients with the more severe forms of NAFLD and may serve as a noninvasive biomarker to identify patients with NASH.

Nonalcoholic fatty liver disease

No effective medical interventions exist that completely reverse the disease other than lifestyle changes, dietary alterations and, possibly, bariatric surgery, however, several strategies that target pathophysiological processes such as an oversupply of fatty acids to the liver, cell injury and inflammation are currently under investigation.

BMP Signalling at the Crossroad of Liver Fibrosis and Regeneration

This review focus on the liver as a target tissue for BMPs actions on regulation of the liver regenerative response to various insults, either acute or chronic and their effects on development and progression of liver fibrosis in different pathological conditions.
...