S-Space Graduate School of Convergence Science and Technology (융합과학기술대학원) Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과) Theses (Master's Degree_분자의학 및 바이오제약학과)
The AMPK activators, HL156A and HL176OUT04 reduce thioacetamide-induced hepatic fibrosis via the inhibition of hepatic stellate cell activation
AMPK activator인 HL156A와 HL176OUT04의 간성상세포 활성화 억제를 통한 TAA 유발 간섬유화 감소 효과 연구
- 융합과학기술대학원 분자의학 및 바이오제약학과
- Issue Date
- 서울대학교 융합과학기술대학원
- 학위논문 (석사)-- 서울대학교 융합과학기술대학원 : 분자의학및바이오제약학과, 2016. 8. 이호영.
- Chronic liver injury caused by many etiological factors, toxins, disturbance of the immune system leads to hepatic fibrosis. Hepatic fibrosis bring about activation of hepatic stellate cells(HSCs), playing significant roles in the development of hepatic fibrosis and excessive accumulation of the extracellular matrix(ECM) proteins, such as collagens mediated by matrix metalloproteinase(MMPs) and tissue inhibitors of metalloproteinases(TIMPs).
In responses liver injury, hepatic stellate cells transforming from a quiescent form to a activated form. Activated hepatic stellate cells causes progression of the liver fibrosis and increase expression of the α-smooth muscle actin(α-SMA), a major marker of HSCs activation and liver fibrosis. HL156A and HL176OUT04, which are noble biguanide derivatives and based on metformin formula. HL156A and HL176OUT04 are widely known that activate AMP-activated protein kinase(AMPK). But function of thE HL156A and HL176OUT04 in liver are poorly understood. Therefore we investigated that anti-fibrotic effects of the HL156A and HL176OUT04 in liver. To investigate that antifibrotic effect on liver fibrosis of HL156A and HL176OUT04, we inject thioacetamide with HL156A and HL176OUT04 in mouse. As a result, we found that HL156A and HL176OUT04 reduce fibrosis marker, collagen, α-SMA in mouse liver. And we treat with HL156A and HL176OUT04 in hepatic stellate cells, whtich are activated by treated TGF-β. Then we found that HL156A and HL176OUT04 inhibit α-SMA expression in hepatic stellate cells.
These results suggest that HL156A and HL176OUT04 inhibit activation of hepatic stellate cells and reduce hepatic fibrosis. Therefore HL156A and HL176OUT04 can be applied to the anti-fibrotic therapy.