# Angiotensin II Activates Yes-Associated Protein (YAP) in Fibroblast Promoting Deep Fascia Remodeling

## TL;DR

This study shows that Angiotensin II activates YAP in fascial fibroblasts, leading to fibrotic changes in deep fascia, suggesting a new pathway for treating fibrosis.

## Contribution

The discovery of a novel Ang II–YAP signaling pathway in deep fascia fibroblasts that promotes fibrotic remodeling.

## Key findings

- Ang II activates YAP in fascial fibroblasts through AT1R, causing YAP nuclear translocation.
- Prolonged Ang II exposure increases fibrosis-related gene expression, which is reduced by AT1R or YAP inhibitors.
- Ang II promotes fibroblast proliferation and migration via AT1R-dependent pathways.

## Abstract

The deep fascia, traditionally regarded as a passive structural tissue, is now recognized as a metabolically and biologically active structure where biochemical signals and biomechanical forces interact to influence proprioception, pain, force transmission, and adaptation to mechanical load. In this study, the convergence point between Angiotensin II (Ang II) signaling via its receptor, Angiotensin type 1 receptor (AT1R), and the mechanosensor Yes-associated protein (YAP) was investigated in human fascial fibroblasts. The presence of angiotensin II (Ang II) receptors was confirmed in fibroblasts from the deep fascia, with the AT1 receptor being the most prevalent subtype. Short-term exposure to Ang II (15–30 min) caused YAP dephosphorylation and its translocation to the nucleus, indicating YAP activation. Notably, prolonged Ang II treatment (7 days) significantly increased the expression of fibrosis-related genes, including collagen types I and III (COL1A1, COL3A1), and hyaluronan binding protein 2 (HABP2). This gene expression was decreased by pretreatment with the AT1R antagonist irbesartan or the YAP inhibitor verteporfin. Additionally, Ang II promoted fibroblast proliferation/migration, key features of fibrotic progression, through AT1R-dependent pathways. These findings show that Ang II acts as both a biochemical and biomechanical signal in the deep fascia, activating YAP signaling and promoting fibrotic remodeling. Our results uncover a new Ang II–YAP pathway in fascial fibroblasts, offering potential targets for therapy in fibrosis and related conditions involving the deep fascia.