Chondroitin sulfate mediates liver responses to injury induced by dual endothelin receptor inhibition.

In this study we investigated whether dual ER inhibition in the liver could alter CHST3 and CHST13 expression and thus CS production, and whether liver CS content could prevent inflammatory and fibrosis responses after liver injury. We observed increased CHST3 and CHST13 expression after liver injury in bile duct-ligated mice and histologically confirmed abundant CS deposition in the injured liver. Moreover, treating Hep3B cells with a dual ERA mimic significantly increased CHST3 and CHST13 expression, inflammatory cytokine levels, and glycosaminoglycan deposition. Furthermore, pro-inflammatory and pro-fibrotic markers were observed after dual ERA treatment, while treatment with CS-degrading chondroitinase ABC was able to successfully reverse these phenotypes. These observations suggest that CHST3 and CHST13-induced CS production can mediate liver injury responses caused by dual ER inhibition, thus could be an alternative pathway for treating ERA-induced liver injury. PMID: 32315540 [PubMed - as supplied by publisher]
Source: Canadian Journal of Physiology and Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Can J Physiol Pharmacol Source Type: research