Transforming growth factor-beta 1 (TGF-β1) is a critical cytokine that plays a pivotal role in a wide range of biological processes, including cell growth, differentiation, migration, apoptosis, and immune regulation. In mice, TGF-β1 is predominantly secreted in a latent form, which requires activation to exert its biological effects. The latent form of TGF-β1 (L-TGF-β1) is composed of the mature TGF-β1 molecule, the latency-associated peptide (LAP), and the latent TGF-β1-binding protein (LTBP). This complex structure ensures that TGF-β1 is stored in the extracellular matrix (ECM) and can be activated in response to specific cellular and mechanical cues.
The mechanical activation of latent TGF-β1 is a critical mechanism by which cells can modulate TGF-β1 signaling. Forces exerted on the latency-associated peptide (LAP) through integrins can lead to conformational changes in the latent complex, resulting in the release of active TGF-β1. This process is more efficient under conditions of higher cell forces and ECM stiffening, highlighting the importance of mechanical cues in TGF-β1 activation