Study on the physiological and pathological function of highly-sufated chondroitin/dermatan sulfate

2014 Fiscal Year Final Research Report

• Project/Area Number: 23570175
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Aichi Medical University
• Principal Investigator: HABUCHI Osami 愛知医科大学, 公私立大学の部局等, その他 (90024067)
• Co-Investigator(Renkei-kenkyūsha): HABUCHI Hiroko 愛知医科大学, 公私立大学の部局等, その他 (90329821)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Keywords: コンドロイチン硫酸 / デルマタン硫酸 / GalNAc4S-6ST / 肝繊維化 / デコリン / MMP / 骨密度

Outline of Final Research Achievements

GalNAc4S-6ST transfers sulfate to position 6 of GalNAc(4SO4) in chondroitin sulfate (CS) or dermatan sulfate (DS) to yield GalNAc(4,6-SO4) residues. We found previously that highly sulfated DS (DS-E) containing GalNAc(4,6-SO4) are present in the mouse liver as GAG chains of decorin and/or biglycan. To determine if DS-E plays a role in liver fibrosis, we compared liver fibrosis induced by CCl4 between GalNAc4S-6ST KO mice (DS-E deficient) and WT mice. ALT and AP activities after injection of CCl4 were higher in KO mice than in WT mice. The amount of collagen was higher in KO mice than in WT mice on 6 week and later after cessation of CCl4 injection. Among MMPs, expressions MMP-9 (both mRNA and enzyme activity) were lower in KO mice than in WT mice. These results suggest that in the absence of DS-E, liver fibrosis induced by CCl4 was more severe and the healing process was delayed.
Deficient in CS-E caused decrease in bone density through abnormal differentiation of osteoblasts.

Free Research Field

生化学