Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.1.6.4 (
chondroitinase
)
2,039
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Although dual endothelin receptor antagonists (ERAs) show great promise for treating various conditions, their propensity to induce liver injury limits their clinical usage. Inflammation and fibrosis are important processes in liver responses to injury and it has been suggested that they and dual ERA-induced liver injury are mediated by the proteoglycan component chondroitin sulfate (CS), which is synthesized by
CHST3
and
CHST13
. 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 and thus could be an alternative pathway for treating ERA-induced liver injury.
...
PMID:Chondroitin sulfate mediates liver responses to injury induced by dual endothelin receptor inhibition. 3231 40
