Natural agents with antifibrotic properties: The hormone relaxin
Relaxin (RLX) is an heterodimeric polypeptidic hormone that belongs to the insulin-like superfamily. Three human genes coding for H1, H2 and H3 relaxin have been identified. In women, the H2 gene is expressed in the corpus luteum, endometrium, placenta, and breast, while H1 mRNA has been found in the placenta only. In men, H1 and H2 expression has been reported in the prostate gland and seminal vesicles. In vitro and in vivo studies of exogenous RLX administration have shown a substantial reduction in collagen production and tissue metalloproteinase inhibitor-1 and 2 (TIMP-1, TIMP-2) expression by dermal and lung fibroblasts and by hepatic stellate cells. The role of RLX in fibrostenotic Crohn's disease is also under investigation. One of the hypotheses in fibrosis suggests that progression of fibrosis results from increased synthesis of extracellular matrix molecules along with elevated expression of TIMP-1 and 2 which inhibit matrix degradation. Consequently, antifibrotic therapies must target towards either reducing matrix synthesis or/and increasing matrix degradation. These promising data for RLX could be regarded nowadays as a point of interest in trials for every disease that is pathophysiologically linked with fibrotic or fibrostenotic procedures due to abnormal collagen accumulation or collagen degradation.