Balance and circumstance: The renin angiotensin system in wound healing and fibrosis

The tissue renin angiotensin system (tRAS) is a locally-acting master-modulator of tissue homeostasis and regeneration. Through these abilities, it is emerging as an attractive target for therapies aiming to restore tissue homeostasis in conditions associated with disturbed wound healing. The tRAS can be divided into two axes - one being pro-inflammatory and pro-fibrotic and one being anti-inflammatory and anti-fibrotic. However, the division of the axes is fuzzy and imperfect as the axes are codependent and the outcome of tRAS activation is determined by the context. Although the tRAS is a local system it shares its key enzymes, ligands and receptors with the systemic RAS and is consequently also targeted by repurposing of drugs developed against the systemic RAS to manage hypertension. With a focus on the skin we will here discuss the tRAS, its involvement in physiological and pathological wound healing, and the therapeutic aptitude of its targeting to treat chronic wounds and fibrosis.