Pathogenic integrins

Pathogenic integrins refer to a specialized subset of the integrin family of heterodimeric cell surface receptors that are primarily characterized by their role in driving disease states such as tissue fibrosis, cancer, and chronic inflammation. Unlike homeostatic integrins that maintain normal tissue architecture and cell signaling, pathogenic members—most notably alpha-v beta-1 (avb1), alpha-v beta-6 (avb6), and alpha-v beta-8 (avb8)—are typically upregulated in response to injury or within the tumor microenvironment. Their primary pathological mechanism involves the localized, mechanical activation of latent Transforming Growth Factor-beta (TGF-beta), a potent cytokine that promotes myofibroblast differentiation and excessive extracellular matrix deposition in organs like the lungs, liver, and kidneys. In oncology, these integrins contribute to the epithelial-mesenchymal transition (EMT), enhance tumor cell invasion, and facilitate an immunosuppressive environment. Therapeutic strategies targeting pathogenic integrins, such as small molecule inhibitors and monoclonal antibodies, aim to selectively block these disease-driving interactions while sparing the essential physiological functions of the broader integrin family.

Other names

Fibrotic integrinsTGF-beta activating integrinsAlpha-v integrins (pathogenic subset)Tumor-associated integrins

Competitive inhibition of ligand binding (e.g., RGD motif) and blockade of integrin-mediated mechanical activation of latent TGF-beta.