Title:Human Recombinant Relaxin (Serelaxin) as Anti-fibrotic Agent: Pharmacology, Limitations and Actual Perspectives
Volume: 22
Issue: 3
Author(s): Chiara Sassoli, Silvia Nistri, Flaminia Chellini and Daniele Bani*
Affiliation:
- Research Unit of Histology & Embryology, University of Florence, Florence, Italy
Keywords:
Connective tissue, extracellular matrix (ECM), fibrosis, myofibroblasts, relaxin (RLX), RXFP1, sereleaxin, TGF-β.
Abstract: Relaxin (recombinant human relaxin-2 hormone; RLX-2; serelaxin) had raised
expectations as a new medication for fibrotic diseases. A plethora of in vitro and in vivo
studies have offered convincing demonstrations that relaxin promotes remodeling of
connective tissue extracellular matrix mediated by inhibition of multiple fibrogenic
pathways, especially the downstream signaling of transforming growth factor (TGF)-β1,
a major pro-fibrotic cytokine, and the recruitment and activation of myofibroblasts, the
main fibrosis-generating cells. However, all clinical trials with relaxin in patients with
fibrotic diseases gave inconclusive results. In this review, we have summarized the
molecular mechanisms of fibrosis, highlighting those which can be effectively targeted
by relaxin. Then, we have performed a critical reappraisal of the clinical trials performed
to date with relaxin as an anti-fibrotic drug, in order to highlight their key points of
strength and weakness and to identify some future opportunities for the therapeutic use
of relaxin, or its analogues, in fibrotic diseases and pathologic scarring which, in our
opinion, deserve to be investigated.
