NASH Target Development Service for Integrin α_vβ₆

Integrin αᵥβ₆ might be a novel target for the hepatic fibrosis and non-alcoholic steatohepatitis (NASH) treatment since it is a special epithelial transmembrane receptor relevant to multiple fibrosis through mediation the activation of TGF-β1. Creative Biolabs offers a series of scientific research services about integrin αᵥβ₆ for the NASH target discovery to global customers.

Introduction to Integrin α_vβ₆

Integrins are a class of transmembrane cell surface receptors expressed by most cells, which promote cell-cell or cell-extracellular matrix (ECM) attachment. The integrin family consists of two non-covalently associated transmembrane glycoproteins α and β subunits. There are 18 α subunit and 8 β subunit genes in mammalian cells, of which 24 different integrins with different functions and ligands recognition can be formed by their various combinations. Integrin αᵥβ₆ is an epithelial-specific integrin that is composed of αᵥ and β₆ subunits. Integrin αᵥβ₆ is the receptor for several ligands, such as latency-associated peptide, fibronectin, transforming growth factor β1 (TGF-β1) and tenascin. Unlike other integrins, integrin αᵥβ₆ is non-existent or poorly expressed in healthy adult epithelial cells, but is upregulated in wound healing, cancer, and certain fibrotic disorders. Integrin αᵥβ₆ is an important molecule with many bioactivities such as TGF-β1 activation, modulate invasion, apoptosis inhibition, immune surveillance, etc.

Fig.1 Schematics of integrins. (Dong, 2018)

Integrin α_vβ₆ Inhibition for NASH Treatment

Integrins exert their functions primarily by attaching of the cell to the ECM and thereby activating signal transduction pathways that mediate diverse cellular activities. Abnormal expression of integrins associates with a series of disorders, such as fibrosis, infections, cancers and so forth. As described before, integrin α_vβ₆ can’t be detected in normal adult liver. Therefore, upregulation or overexpression of integrin α_vβ₆ in the liver may be an indicator of hepatic fibrosis. The expression of integrin α_vβ₆ was markedly increased not only in mouse fibrosis but also in human hepatitis fibrosis, cirrhosis, and other liver injuries. Studies suggested that integrin α_vβ₆ is a promising pharmacological target of liver fibrosis, which probably was implicated in integrin α_vβ₆-mediated activation of TGF-β1.

β₆-blocking antibodies, anti-integrin α_vβ₆ antibodies, and integrin antagonists can suppress α_vβ₆-mediated TGF-β1 activation, which presents protective and anti-fibrogenic effects on liver fibrosis. And integrin α_vβ₆ inhibition by these antibodies or antagonists is a potential hepatic fibrosis as well as NASH therapeutic strategy.

Fig.2 Integrin α_vβ₆ as an indirect mediator of liver fibrosis progression. (Patsenker, 2011)

In terms of NASH target discovery and therapeutic strategies development, Creative Biolabs has established specialized scientist teams and comprehensive platforms (e.g. Hit to Lead, Lead Optimization, IND-Enabling, Target Identification, and Validation, Hit identification) to provide first-in-class services, which include but not limited to:

• Biomarkers for NASH Diagnosis
• Target Discovery and Therapeutic Strategies
• Preclinical Models of NASH

Just feel free to contact us for more detailed communications and information. Our scientists can tailor NASH treatment services according to your needs.

References

1. Dong, X.C; et al. High integrin α_vβ₆ affinity reached by hybrid domain deletion slows ligand-binding on-rate. Proceedings of the National Academy of Sciences of the United States of America. 2018, 115(7): E1429-E1436.
2. Patsenker, E.; Stickel, F. Role of integrins in fibrosing liver diseases. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2011, 301(3): G425-G434.