PRIYANKA CHAKRABORTY, AMITY UNIVERSITY, KOLKATA
Liver fibrosis is one of the leading causes of morbidity and mortality among human beings. The unavailability of proper antifibrotic therapy makes the disease more deadly and the patients more vulnerable. RLX ( peptide hormone human relaxin-2), acting through a G protein-coupled receptor relaxin peptide receptor 1 (RXFP1), promotes tissue rebuilding and is antifibrotic over most major organs. Therefore, mice without RLX develop rigorous fibrotic diseases with old age, completely opposed by treatment with recombinant RLX.
Scientists have used lipid nano-particles coupled with aminoethyl anis-amide, a critical ligand for the sigma-1 receptor expressed on activated HSC (Hepatic stellate cells), resulting in a targeted increase in RLX levels and striking retardation of fibrosis backing chronic liver injury. Notably, scientists identified crucial immunomodulatory effects of RLX, resulting in an increase of hepatic restorative macrophages and a marginal reduction in fibrosis.
Macrophages and monocytes have long been called a key controller of hepatic fibrosis and represent a positive pharmacological target. Therefore, monocyte recruitment in patients with liver fibrosis may hinder matrix construction. Hence, a therapeutic approach aimed at instituting macrophage phenotype in situ to govern pro-fibrotic characters and enhance restorative properties is extremely attractive, although so far been elusive.
The major challenges in converting pre-clinical data from sample models into tractable treatments are the lack of comparative analyses in relevant human models. This information is also of broader regard as there are many other positive development opportunities, for RLX-based therapeutics, beyond fibrosis, including acute kidney injury/hepatorenal syndrome, musculoskeletal conditions, and many more. Nevertheless, this study provides a new method to use the intrinsic tissue construction properties of RLX that have excited researchers ever since its discovery.
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Citation:Fallowfield, J.A., Ramachandran, P. A relaxin-based nanotherapy for liver fibrosis. Nat. Nanotechnol. (2021). https://doi.org/10.1038/s41565-020-00832-w
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