Targeting the Wnt Signaling Pathway in Liver Fibrosis for Drug Options: An Update

Duspara, Kristina; Bojanić, Kristina; Pejic, Josipa Ivanusic; Kuna, Lucija; Kolarić, Tea Omanović; Ninčević, Vjera; Stoehr, Robert; Včev, Aleksandar; Glasnović, Marija; Bilić-Ćurčić, Ines; Smolić, Martina

doi:10.14218/jcth.2021.00065

Cited by 22 publications

(18 citation statements)

References 119 publications

(240 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It should be noted that Wnt activation-induced fibrotic illness was more significant than the impacts of other fibrotic pathways. The canonical Wnt pathway’s activation and the strong profibrotic effects it has led some researchers to hypothesize that the Wnt pathway might be a potential target for novel antifibrotic approaches [ 108 ].…”

Section: Role Of Wnt Pathway In Fibrosismentioning

confidence: 99%

Fibrosis: Types, Effects, Markers, Mechanisms for Disease Progression, and Its Relation with Oxidative Stress, Immunity, and Inflammation

Antar

Ashour

Marawan

et al. 2023

IJMS

View full text Add to dashboard Cite

Most chronic inflammatory illnesses include fibrosis as a pathogenic characteristic. Extracellular matrix (ECM) components build up in excess to cause fibrosis or scarring. The fibrotic process finally results in organ malfunction and death if it is severely progressive. Fibrosis affects nearly all tissues of the body. The fibrosis process is associated with chronic inflammation, metabolic homeostasis, and transforming growth factor-β1 (TGF-β1) signaling, where the balance between the oxidant and antioxidant systems appears to be a key modulator in managing these processes. Virtually every organ system, including the lungs, heart, kidney, and liver, can be affected by fibrosis, which is characterized as an excessive accumulation of connective tissue components. Organ malfunction is frequently caused by fibrotic tissue remodeling, which is also frequently linked to high morbidity and mortality. Up to 45% of all fatalities in the industrialized world are caused by fibrosis, which can damage any organ. Long believed to be persistently progressing and irreversible, fibrosis has now been revealed to be a very dynamic process by preclinical models and clinical studies in a variety of organ systems. The pathways from tissue damage to inflammation, fibrosis, and/or malfunction are the main topics of this review. Furthermore, the fibrosis of different organs with their effects was discussed. Finally, we highlight many of the principal mechanisms of fibrosis. These pathways could be considered as promising targets for the development of potential therapies for a variety of important human diseases.

show abstract

Section: Role Of Wnt Pathway In Fibrosismentioning

confidence: 99%

Fibrosis: Types, Effects, Markers, Mechanisms for Disease Progression, and Its Relation with Oxidative Stress, Immunity, and Inflammation

Antar

Ashour

Marawan

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

“…Blockage of components of this pathway may be effective for stopping the progression of liver fibrosis or cancer. However, there is also evidence that this pathway maintains HSCs in a quiescent state, suggesting anti-fibrotic activities as well [ 124 ]. The Wnt pathway, moreover, contributes to obesity and the expansion of white adipose tissues [ 125 ].…”

Section: Bambi and The Wnt/β-catenin Pathwaymentioning

confidence: 99%

“…There is ample of evidence that BAMBI is upregulated by the Wnt pathway which in turn is activated by BAMBI. The Wnt pathway is activated in chronic liver injury and contributes to inflammation, the proliferation of HSCs, and fibrosis [ 124 ]. BAMBI protein is, however, low in almost all experimental models of hepatic injury ( Figure 5 ), and this suggests that pathways contributing to BAMBI suppression are much more relevant in vivo.…”

Section: Bambi and The Wnt/β-catenin Pathwaymentioning

confidence: 99%

Expression and Function of BMP and Activin Membrane-Bound Inhibitor (BAMBI) in Chronic Liver Diseases and Hepatocellular Carcinoma

Weber

Treeck²,

Mester

et al. 2023

IJMS

View full text Add to dashboard Cite

BAMBI (bone morphogenetic protein and activin membrane-bound inhibitor) is a transmembrane pseudoreceptor structurally related to transforming growth factor (TGF)-β type 1 receptors (TGF-β1Rs). BAMBI lacks a kinase domain and functions as a TGF-β1R antagonist. Essential processes such as cell differentiation and proliferation are regulated by TGF-β1R signaling. TGF-β is the best-studied ligand of TGF-βRs and has an eminent role in inflammation and fibrogenesis. Liver fibrosis is the end stage of almost all chronic liver diseases, such as non-alcoholic fatty liver disease, and at the moment, there is no effective anti-fibrotic therapy available. Hepatic BAMBI is downregulated in rodent models of liver injury and in the fibrotic liver of patients, suggesting that low BAMBI has a role in liver fibrosis. Experimental evidence convincingly demonstrated that BAMBI overexpression is able to protect against liver fibrosis. Chronic liver diseases have a high risk of hepatocellular carcinoma (HCC), and BAMBI was shown to exert tumor-promoting as well as tumor-protective functions. This review article aims to summarize relevant studies on hepatic BAMBI expression and its role in chronic liver diseases and HCC.

show abstract

“…In the end, the proteasome breaks down b-catenin. When Wnt signaling is active, Wnt-Fz and LRP work together to coordinate the activation of Dvl, which causes the multiprotein complex to dissociate and inactivate GSK-3b (no phosphorylation) [ 21 ]. Excessive free b-catenin translocates to the nucleus and binds to TCF/LEF transcription factors, resulting in transcriptional activation of Wnt target genes.…”

Section: Molecules and Mechanisms Of Liver Fibrosismentioning

confidence: 99%

The Molecular Mechanisms of Liver Fibrosis and Its Potential Therapy in Application

Zhang

Sun

2022

IJMS

View full text Add to dashboard Cite

Liver fibrosis results from repeated and persistent liver damage. It can start with hepatocyte injury and advance to inflammation, which recruits and activates additional liver immune cells, leading to the activation of the hepatic stellate cells (HSCs). It is the primary source of myofibroblasts (MFs), which result in collagen synthesis and extracellular matrix protein accumulation. Although there is no FDA and EMA-approved anti-fibrotic drug, antiviral therapy has made remarkable progress in preventing or even reversing the progression of liver fibrosis, but such a strategy remains elusive for patients with viral, alcoholic or nonalcoholic steatosis, genetic or autoimmune liver disease. Due to the complexity of the etiology, combination treatments affecting two or more targets are likely to be required. Here, we review the pathogenic mechanisms of liver fibrosis and signaling pathways involved, as well as various molecular targets for liver fibrosis treatment. The development of efficient drug delivery systems that target different cells in liver fibrosis therapy is also summarized. We highlight promising anti-fibrotic events in clinical trial and preclinical testing, which include small molecules and natural compounds. Last, we discuss the challenges and opportunities in developing anti-fibrotic therapies.

show abstract

Targeting the Wnt Signaling Pathway in Liver Fibrosis for Drug Options: An Update

Cited by 22 publications

References 119 publications

Fibrosis: Types, Effects, Markers, Mechanisms for Disease Progression, and Its Relation with Oxidative Stress, Immunity, and Inflammation

Fibrosis: Types, Effects, Markers, Mechanisms for Disease Progression, and Its Relation with Oxidative Stress, Immunity, and Inflammation

Expression and Function of BMP and Activin Membrane-Bound Inhibitor (BAMBI) in Chronic Liver Diseases and Hepatocellular Carcinoma

The Molecular Mechanisms of Liver Fibrosis and Its Potential Therapy in Application

Contact Info

Product

Resources

About