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Chitinase 3-like 1 deficiency ameliorates liver fibrosis by promoting hepatic macrophage apoptosis
- Source :
- Hepatology Research
- Publication Year :
- 2019
-
Abstract
- Aim Chitinase 3-like 1 (CHI3L1), an 18-glycosyl hydrolase-related molecule, is a member of the enzymatically inactive chitinase-like protein family. Serum levels of CHI3L1 are strongly correlated with hepatic fibrosis progression during many liver diseases. Therefore, this protein could be involved in the development of hepatic fibrosis pathology; however, its role has not been elucidated. We aimed to elucidate its role in the pathophysiology of liver fibrosis. Methods Chitinase 3-like 1-deficient (Chi3l1-/- ) mice were given carbon tetrachloride twice per week for 4 weeks or fed a methionine choline-deficient diet for 12 weeks to generate mouse liver fibrosis models. Human fibrotic liver tissues were also examined immunohistochemically. Results In human and mouse fibrotic livers, CHI3L1 expression was mainly localized to hepatic macrophages, and the intrahepatic accumulation of CHI3L1+ macrophages was significantly enhanced compared to that in control livers. In the two mouse models, hepatic fibrosis was significantly ameliorated in Chi3l1-/- mice compared to that in wild-type mice, which was dependent on hepatic macrophages. The accumulation and activation of hepatic macrophages was also significantly suppressed in Chi3l1-/- mice compared to that in wild-type mice. Furthermore, apoptotic hepatic macrophages were significantly increased in Chi3l1-/- mice. Chitinase 3-like 1 was found to inhibit hepatic macrophage apoptosis by suppressing Fas expression and activating Akt signaling in an autocrine manner, which resulted in hepatic macrophage accumulation and activation, exaggerating liver fibrosis. Conclusions Chitinase 3-like 1 exacerbates liver fibrosis progression by suppressing apoptosis in hepatic macrophages. Therefore, this might be a potential therapeutic target for the treatment of liver fibrosis.
- Subjects :
- Hepatology
Chemistry
Akt
Original Articles
macrophage
Fas
CHI3L1
Pathophysiology
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Infectious Diseases
Apoptosis
030220 oncology & carcinogenesis
Cancer research
Carbon tetrachloride
Macrophage
030211 gastroenterology & hepatology
Original Article
Autocrine signalling
Hepatic fibrosis
chitinase 3‐like 1
Protein kinase B
liver fibrosis
Subjects
Details
- ISSN :
- 13866346
- Volume :
- 49
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Hepatology research : the official journal of the Japan Society of Hepatology
- Accession number :
- edsair.doi.dedup.....f941041df2a08933f17d768233c00e6a