The effects of relaxin on extracellular matrix remodeling in health and fibrotic disease.
Since its discovery as a reproductive hormone 80 years ago, relaxin has been implicated in a number of pregnancy-related functions involving extracellular matrix (ECM) turnover and collagen degradation. It is now becoming evident that relaxin's ability to reduce matrix synthesis and increase ECM degradation has important implications in several nonreproductive organs, including the heart, lung, kidney, liver and skin. The identification of relaxin and RXFP1 (Relaxin family peptide receptor-1) mRNA and/or binding sites in cells or vessels of these nonreproductive tissues, has confirmed them as targets for relaxin binding and activity. Recent studies on Rln1 and Rxfp1 gene-knockout mice have established relaxin as an important naturally occurring and protective moderator of collagen turnover, leading to improved organ structure and function. Furthermore, through its ability to regulate the ECM and in particular, collagen at multiple levels, relaxin has emerged as a potent anti-fibrotic therapy, with rapid-occurring efficacy. It not only prevents fibrogenesis, but also reduces established scarring (fibrosis), which is a leading cause of organ failure and affects several tissues regardless of etiology. This chapter will summarize these coherent findings as a means of highlighting the significance and therapeutic potential of relaxin.
Samuel
Chrishan S
CS
Howard Florey Institute, University of Melbourne, Parkville, Victoria 3010, Australia. chrishan.samuel@florey.edu.au
Lekgabe
Edna D
ED
Mookerjee
Ishanee
I
D000818:Animals; D002921:Cicatrix / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D003094:Collagen / Q000378:metabolism*; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005355:Fibrosis; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009928:Organ Specificity; D011247:Pregnancy; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D018000:Receptors, Peptide; D012065:Relaxin / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use
D008565:Membrane Proteins; C095067:RLN1 protein, human; C417543:RXFP1 protein, human; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; C492607:Rln1 protein, mouse; D012065:Relaxin; D003094:Collagen