Relaxin as an anti-fibrotic treatment: Perspectives, challenges and future directions

[Display omitted] Fibrosis refers to the scarring and hardening of tissues, which results from a failed immune system-coordinated wound healing response to chronic organ injury and which manifests from the aberrant accumulation of various extracellular matrix components (ECM), primarily collagen. Despite being a hallmark of prolonged tissue damage and related dysfunction, and commonly associated with high morbidity and mortality, there are currently no effective cures for its regression. An emerging therapy that meets several criteria of an effective anti-fibrotic treatment, is the recombinant drug-based form of the human hormone, relaxin (also referred to as serelaxin, which is bioactive in several other species). This review outlines the broad anti-fibrotic and related organ-protective roles of relaxin, mainly from studies conducted in preclinical models of ageing and fibrotic disease, including its ability to ameliorate several aspects of fibrosis progression and maturation, from immune cell infiltration, pro-inflammatory and pro-fibrotic cytokine secretion, oxidative stress, organ hypertrophy, cell apoptosis, myofibroblast differentiation and ECM production, to its ability to facilitate established ECM degradation. Studies that have compared and/or combined these therapeutic effects of relaxin with current standard of care medication have also been discussed, along with the main challenges that have hindered the translation of the anti-fibrotic efficacy of relaxin to the clinic. The review then outlines the future directions as to where scientists and several pharmaceutical companies that have recognized the therapeutic potential of relaxin are working towards, to progress its development as a treatment for human patients suffering from various fibrotic diseases.